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Published in: BMC Cancer 1/2012

Open Access 01-12-2012 | Research article

Enhanced expression of G-protein coupled estrogen receptor (GPER/GPR30) in lung cancer

Authors: Venkatakrishna Rao Jala, Brandie N Radde, Bodduluri Haribabu, Carolyn M Klinge

Published in: BMC Cancer | Issue 1/2012

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Abstract

Background

G-protein-coupled estrogen receptor (GPER/GPR30) was reported to bind 17β-estradiol (E2), tamoxifen, and ICI 182,780 (fulvestrant) and promotes activation of epidermal growth factor receptor (EGFR)-mediated signaling in breast, endometrial and thyroid cancer cells. Although lung adenocarcinomas express estrogen receptors α and β (ERα and ERβ), the expression of GPER in lung cancer has not been investigated. The purpose of this study was to examine the expression of GPER in lung cancer.

Methods

The expression patterns of GPER in various lung cancer lines and lung tumors were investigated using standard quantitative real time PCR (at mRNA levels), Western blot and immunohistochemistry (IHC) methods (at protein levels). The expression of GPER was scored and the pairwise comparisons (cancer vs adjacent tissues as well as cancer vs normal lung tissues) were performed.

Results

Analysis by real-time PCR and Western blotting revealed a significantly higher expression of GPER at both mRNA and protein levels in human non small cell lung cancer cell (NSCLC) lines relative to immortalized normal lung bronchial epithelial cells (HBECs). The virally immortalized human small airway epithelial cell line HPL1D showed higher expression than HBECs and similar expression to NSCLC cells. Immunohistochemical analysis of tissue sections of murine lung adenomas as well as human lung adenocarcinomas, squamous cell carcinomas and non-small cell lung carcinomas showed consistently higher expression of GPER in the tumor relative to the surrounding non-tumor tissue.

Conclusion

The results from this study demonstrate increased GPER expression in lung cancer cells and tumors compared to normal lung. Further evaluation of the function and regulation of GPER will be necessary to determine if GPER is a marker of lung cancer progression.
Appendix
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Literature
1.
go back to reference Siegel R, Ward E, Brawley O, Jemal A: Cancer statistics, 2011. CA Cancer J Clin. 2011, 61: 212-236.CrossRefPubMed Siegel R, Ward E, Brawley O, Jemal A: Cancer statistics, 2011. CA Cancer J Clin. 2011, 61: 212-236.CrossRefPubMed
2.
go back to reference Ramchandran K, Patel JD: Sex Differences in Susceptibility to Carcinogens. Semin Oncol. 2009, 36: 516-523.CrossRefPubMed Ramchandran K, Patel JD: Sex Differences in Susceptibility to Carcinogens. Semin Oncol. 2009, 36: 516-523.CrossRefPubMed
3.
go back to reference Kiyohara C, Ohno Y: Sex differences in lung cancer susceptibility: a review. Gender Medicine. 2010, 7: 381-401.CrossRefPubMed Kiyohara C, Ohno Y: Sex differences in lung cancer susceptibility: a review. Gender Medicine. 2010, 7: 381-401.CrossRefPubMed
4.
go back to reference Bouchardy C, Benhamou S, Schaffar R, Verkooijen HM, Fioretta G, Schubert H, Vinh-Hung V, Soria J-C, Vlastos G, Rapiti E: Lung cancer mortality risk among breast cancer patients treated with anti-estrogens. Cancer. 2011, 117: 1288-1295.CrossRefPubMed Bouchardy C, Benhamou S, Schaffar R, Verkooijen HM, Fioretta G, Schubert H, Vinh-Hung V, Soria J-C, Vlastos G, Rapiti E: Lung cancer mortality risk among breast cancer patients treated with anti-estrogens. Cancer. 2011, 117: 1288-1295.CrossRefPubMed
5.
go back to reference Dubey S, Siegfried JM, Traynor AM: Non-small-cell lung cancer and breast carcinoma: chemotherapy and beyond. Lancet Oncol. 2006, 7: 416-424.CrossRefPubMed Dubey S, Siegfried JM, Traynor AM: Non-small-cell lung cancer and breast carcinoma: chemotherapy and beyond. Lancet Oncol. 2006, 7: 416-424.CrossRefPubMed
6.
go back to reference Pietras RJ, Marquez DC, Chen HW, Tsai E, Weinberg O, Fishbein M: Estrogen and growth factor receptor interactions in human breast and non-small cell lung cancer cells. Steroids. 2005, 70: 372-381.CrossRefPubMed Pietras RJ, Marquez DC, Chen HW, Tsai E, Weinberg O, Fishbein M: Estrogen and growth factor receptor interactions in human breast and non-small cell lung cancer cells. Steroids. 2005, 70: 372-381.CrossRefPubMed
7.
go back to reference Drummond AE, Britt KL, Dyson M, Jones ME, Kerr JB, O'Donnell L, Simpson ER, Findlay JK: Ovarian steroid receptors and their role in ovarian function. Mol Cell Endocrinol. 2002, 191: 27-33.CrossRefPubMed Drummond AE, Britt KL, Dyson M, Jones ME, Kerr JB, O'Donnell L, Simpson ER, Findlay JK: Ovarian steroid receptors and their role in ovarian function. Mol Cell Endocrinol. 2002, 191: 27-33.CrossRefPubMed
8.
go back to reference O'Donnell L, Robertson KM, Jones ME, Simpson ER: Estrogen and spermatogenesis. Endocr Rev. 2001, 22: 289-318.CrossRefPubMed O'Donnell L, Robertson KM, Jones ME, Simpson ER: Estrogen and spermatogenesis. Endocr Rev. 2001, 22: 289-318.CrossRefPubMed
10.
11.
go back to reference Townson SM, O'Connell P: Identification of estrogen receptor alpha variants in breast tumors: implications for predicting response to hormonal therapies. J Surg Oncol. 2006, 94: 271-273.CrossRefPubMed Townson SM, O'Connell P: Identification of estrogen receptor alpha variants in breast tumors: implications for predicting response to hormonal therapies. J Surg Oncol. 2006, 94: 271-273.CrossRefPubMed
12.
go back to reference Cavalieri E, Frenkel K, Liehr JG, Rogan E, Roy D: Estrogens as endogenous genotoxic agents-DNA adducts and mutations. J Natl Cancer Inst Monogr. 2000, 2000: 75-93.CrossRef Cavalieri E, Frenkel K, Liehr JG, Rogan E, Roy D: Estrogens as endogenous genotoxic agents-DNA adducts and mutations. J Natl Cancer Inst Monogr. 2000, 2000: 75-93.CrossRef
13.
go back to reference Nilsson S, Makela S, Treuter E, Tujague M, Thomsen J, Andersson G, Enmark E, Pettersson K, Warner M, Gustafsson JA: Mechanisms of estrogen action. Physiol Rev. 2001, 81: 1535-1565.PubMed Nilsson S, Makela S, Treuter E, Tujague M, Thomsen J, Andersson G, Enmark E, Pettersson K, Warner M, Gustafsson JA: Mechanisms of estrogen action. Physiol Rev. 2001, 81: 1535-1565.PubMed
14.
go back to reference Zhao C, Gao H, Liu Y, Papoutsi Z, Jaffrey S, Gustafsson J-Å, Dahlman-Wright K: Genome-Wide Mapping of Estrogen Receptor-β–Binding Regions Reveals Extensive Cross-Talk with Transcription Factor Activator Protein-1. Cancer Res. 2010, 70: 5174-5183.CrossRefPubMed Zhao C, Gao H, Liu Y, Papoutsi Z, Jaffrey S, Gustafsson J-Å, Dahlman-Wright K: Genome-Wide Mapping of Estrogen Receptor-β–Binding Regions Reveals Extensive Cross-Talk with Transcription Factor Activator Protein-1. Cancer Res. 2010, 70: 5174-5183.CrossRefPubMed
15.
go back to reference Lumachi F, Luisetto G, Basso SM, Basso U, Brunello A, Camozzi V: Endocrine therapy of breast cancer. Curr Med Chem. 2011, 18: 513-522.CrossRefPubMed Lumachi F, Luisetto G, Basso SM, Basso U, Brunello A, Camozzi V: Endocrine therapy of breast cancer. Curr Med Chem. 2011, 18: 513-522.CrossRefPubMed
16.
go back to reference Kuiper GG, Carlsson B, Grandien K, Enmark E, Haggblad J, Nilsson S, Gustafsson JA: Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta. Endocrinology. 1997, 138: 863-870.PubMed Kuiper GG, Carlsson B, Grandien K, Enmark E, Haggblad J, Nilsson S, Gustafsson JA: Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta. Endocrinology. 1997, 138: 863-870.PubMed
17.
go back to reference Mollerup S, Jorgensen K, Berge G, Haugen A: Expression of estrogen receptors alpha and beta in human lung tissue and cell lines. Lung Cancer. 2002, 37: 153-159.CrossRefPubMed Mollerup S, Jorgensen K, Berge G, Haugen A: Expression of estrogen receptors alpha and beta in human lung tissue and cell lines. Lung Cancer. 2002, 37: 153-159.CrossRefPubMed
18.
go back to reference Stabile LP, Davis AL, Gubish CT, Hopkins TM, Luketich JD, Christie N, Finkelstein S, Siegfried JM: Human non-small cell lung tumors and cells derived from normal lung express both estrogen receptor alpha and beta and show biological responses to estrogen. Cancer Res. 2002, 62: 2141-2150.PubMed Stabile LP, Davis AL, Gubish CT, Hopkins TM, Luketich JD, Christie N, Finkelstein S, Siegfried JM: Human non-small cell lung tumors and cells derived from normal lung express both estrogen receptor alpha and beta and show biological responses to estrogen. Cancer Res. 2002, 62: 2141-2150.PubMed
19.
go back to reference Stabile LP, Lyker JS, Gubish CT, Zhang W, Grandis JR, Siegfried JM: Combined targeting of the estrogen receptor and the epidermal growth factor receptor in non-small cell lung cancer shows enhanced antiproliferative effects. Cancer Res. 2005, 65: 1459-1470.CrossRefPubMed Stabile LP, Lyker JS, Gubish CT, Zhang W, Grandis JR, Siegfried JM: Combined targeting of the estrogen receptor and the epidermal growth factor receptor in non-small cell lung cancer shows enhanced antiproliferative effects. Cancer Res. 2005, 65: 1459-1470.CrossRefPubMed
20.
go back to reference Dougherty SM, Mazhawidza W, Bohn AR, Robinson KA, Mattingly KA, Blankenship KA, Huff MO, McGregor WG, Klinge CM: Gender difference in the activity but not expression of estrogen receptors alpha and beta in human lung adenocarcinoma cells. Endocr Relat Cancer. 2006, 13: 113-134.CrossRefPubMedPubMedCentral Dougherty SM, Mazhawidza W, Bohn AR, Robinson KA, Mattingly KA, Blankenship KA, Huff MO, McGregor WG, Klinge CM: Gender difference in the activity but not expression of estrogen receptors alpha and beta in human lung adenocarcinoma cells. Endocr Relat Cancer. 2006, 13: 113-134.CrossRefPubMedPubMedCentral
21.
go back to reference Ivanova MM, Mazhawidza W, Dougherty SM, Klinge CM: Sex Differences in Estrogen Receptor Subcellular Location and Activity in Lung Adenocarcinoma Cells. Am J Respir Cell Mol Biol. 2010, 42: 320-330.CrossRefPubMed Ivanova MM, Mazhawidza W, Dougherty SM, Klinge CM: Sex Differences in Estrogen Receptor Subcellular Location and Activity in Lung Adenocarcinoma Cells. Am J Respir Cell Mol Biol. 2010, 42: 320-330.CrossRefPubMed
22.
go back to reference Ivanova MM, Mazhawidza W, Dougherty SM, Minna JD, Klinge CM: Activity and intracellular location of estrogen receptors [alpha] and [beta] in human bronchial epithelial cells. Mol Cell Endocrinol. 2009, 205: 12-21.CrossRef Ivanova MM, Mazhawidza W, Dougherty SM, Minna JD, Klinge CM: Activity and intracellular location of estrogen receptors [alpha] and [beta] in human bronchial epithelial cells. Mol Cell Endocrinol. 2009, 205: 12-21.CrossRef
23.
go back to reference Watson CS, Jeng Y-J, Kochukov MY: Nongenomic Signaling Pathways of Estrogen Toxicity. Toxicol Sci. 2010, 115: 1-11.CrossRefPubMed Watson CS, Jeng Y-J, Kochukov MY: Nongenomic Signaling Pathways of Estrogen Toxicity. Toxicol Sci. 2010, 115: 1-11.CrossRefPubMed
24.
go back to reference Jeng Y-J, Kochukov M, Watson C: Membrane estrogen receptor-alpha-mediated nongenomic actions of phytoestrogens in GH3/B6/F10 pituitary tumor cells. J Mol Signal. 2009, 4: 2-CrossRefPubMedPubMedCentral Jeng Y-J, Kochukov M, Watson C: Membrane estrogen receptor-alpha-mediated nongenomic actions of phytoestrogens in GH3/B6/F10 pituitary tumor cells. J Mol Signal. 2009, 4: 2-CrossRefPubMedPubMedCentral
25.
go back to reference Wyckoff MH, Chambliss KL, Mineo C, Yuhanna IS, Mendelsohn ME, Mumby SM, Shaul PW: Plasma membrane estrogen receptors are coupled to endothelial nitric-oxide synthase through Galpha(i). J Biol Chem. 2001, 276: 27071-27076.CrossRefPubMed Wyckoff MH, Chambliss KL, Mineo C, Yuhanna IS, Mendelsohn ME, Mumby SM, Shaul PW: Plasma membrane estrogen receptors are coupled to endothelial nitric-oxide synthase through Galpha(i). J Biol Chem. 2001, 276: 27071-27076.CrossRefPubMed
26.
go back to reference Kelly MJ, Levin ER: Rapid actions of plasma membrane estrogen receptors. Trends Endocrinol Metab. 2001, 12: 152-156.CrossRefPubMed Kelly MJ, Levin ER: Rapid actions of plasma membrane estrogen receptors. Trends Endocrinol Metab. 2001, 12: 152-156.CrossRefPubMed
27.
go back to reference Levin ER: Minireview: Extranuclear Steroid Receptors: Roles in Modulation of Cell Functions. Mol Endocrinol. 2011, 25: 377-384.CrossRefPubMed Levin ER: Minireview: Extranuclear Steroid Receptors: Roles in Modulation of Cell Functions. Mol Endocrinol. 2011, 25: 377-384.CrossRefPubMed
28.
go back to reference Razandi M, Pedram A, Park ST, Levin ER: Proximal events in signaling by plasma membrane estrogen receptors. J Biol Chem. 2003, 278: 2701-2712.CrossRefPubMed Razandi M, Pedram A, Park ST, Levin ER: Proximal events in signaling by plasma membrane estrogen receptors. J Biol Chem. 2003, 278: 2701-2712.CrossRefPubMed
29.
go back to reference Zhang G, Liu X, Farkas AM, Parwani AV, Lathrop KL, Lenzner D, Land SR, Srinivas H: Estrogen Receptor Beta Functions through Non-genomic Mechanisms in Lung Cancer Cells. Mol Endocrinol. 2009, 23: 137-145.CrossRefPubMed Zhang G, Liu X, Farkas AM, Parwani AV, Lathrop KL, Lenzner D, Land SR, Srinivas H: Estrogen Receptor Beta Functions through Non-genomic Mechanisms in Lung Cancer Cells. Mol Endocrinol. 2009, 23: 137-145.CrossRefPubMed
30.
go back to reference Majidi M, Al-Wadei HA, Takahashi T, Schuller HM: Nongenomic beta estrogen receptors enhance beta1 adrenergic signaling induced by the nicotine-derived carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in human small airway epithelial cells. Cancer Res. 2007, 67: 6863-6871.CrossRefPubMed Majidi M, Al-Wadei HA, Takahashi T, Schuller HM: Nongenomic beta estrogen receptors enhance beta1 adrenergic signaling induced by the nicotine-derived carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in human small airway epithelial cells. Cancer Res. 2007, 67: 6863-6871.CrossRefPubMed
31.
go back to reference Levin ER: Cell localization, physiology, and nongenomic actions of estrogen receptors. J Appl Physiol. 2001, 91: 1860-1867.PubMed Levin ER: Cell localization, physiology, and nongenomic actions of estrogen receptors. J Appl Physiol. 2001, 91: 1860-1867.PubMed
32.
go back to reference Audy MC, Vacher P, Duly B: 17 beta-estradiol stimulates a rapid Ca2+ influx in LNCaP human prostate cancer cells. Eur J Endocrinol. 1996, 135: 367-373.CrossRefPubMed Audy MC, Vacher P, Duly B: 17 beta-estradiol stimulates a rapid Ca2+ influx in LNCaP human prostate cancer cells. Eur J Endocrinol. 1996, 135: 367-373.CrossRefPubMed
33.
go back to reference Morley P, Whitfield JF, Vanderhyden BC, Tsang BK, Schwartz JL: A new, nongenomic estrogen action: the rapid release of intracellular calcium. Endocrinology. 1992, 131: 1305-1312.PubMed Morley P, Whitfield JF, Vanderhyden BC, Tsang BK, Schwartz JL: A new, nongenomic estrogen action: the rapid release of intracellular calcium. Endocrinology. 1992, 131: 1305-1312.PubMed
34.
go back to reference Aronica SM, Kraus WL, Katzenellenbogen BS: Estrogen action via the cAMP signaling pathway: stimulation of adenylate cyclase and cAMP-regulated gene transcription. Proc Natl Acad Sci U S A. 1994, 91: 8517-8521.CrossRefPubMedPubMedCentral Aronica SM, Kraus WL, Katzenellenbogen BS: Estrogen action via the cAMP signaling pathway: stimulation of adenylate cyclase and cAMP-regulated gene transcription. Proc Natl Acad Sci U S A. 1994, 91: 8517-8521.CrossRefPubMedPubMedCentral
35.
go back to reference Le Mellay V, Grosse B, Lieberherr M: Phospholipase C beta and membrane action of calcitriol and estradiol. J Biol Chem. 1997, 272: 11902-11907.CrossRefPubMed Le Mellay V, Grosse B, Lieberherr M: Phospholipase C beta and membrane action of calcitriol and estradiol. J Biol Chem. 1997, 272: 11902-11907.CrossRefPubMed
36.
go back to reference Song RX, Santen RJ: Membrane initiated estrogen signaling in breast cancer. Biol Reprod. 2006, 75: 9-16.CrossRefPubMed Song RX, Santen RJ: Membrane initiated estrogen signaling in breast cancer. Biol Reprod. 2006, 75: 9-16.CrossRefPubMed
37.
go back to reference Manavathi B, Kumar R: Steering estrogen signals from the plasma membrane to the nucleus: two sides of the coin. J Cell Physiol. 2006, 207: 594-604.CrossRefPubMed Manavathi B, Kumar R: Steering estrogen signals from the plasma membrane to the nucleus: two sides of the coin. J Cell Physiol. 2006, 207: 594-604.CrossRefPubMed
38.
go back to reference Filardo EJ: Epidermal growth factor receptor (EGFR) transactivation by estrogen via the G-protein-coupled receptor, GPR30: a novel signaling pathway with potential significance for breast cancer. J Steroid Biochem Mol Biol. 2002, 80: 231-238.CrossRefPubMed Filardo EJ: Epidermal growth factor receptor (EGFR) transactivation by estrogen via the G-protein-coupled receptor, GPR30: a novel signaling pathway with potential significance for breast cancer. J Steroid Biochem Mol Biol. 2002, 80: 231-238.CrossRefPubMed
39.
go back to reference Filardo EJ, Quinn JA, Bland KI, Frackelton AR: Estrogen-induced activation of Erk-1 and Erk-2 requires the G protein-coupled receptor homolog, GPR30, and occurs via trans-activation of the epidermal growth factor receptor through release of HB-EGF. Mol Endocrinol. 2000, 14: 1649-1660.CrossRefPubMed Filardo EJ, Quinn JA, Bland KI, Frackelton AR: Estrogen-induced activation of Erk-1 and Erk-2 requires the G protein-coupled receptor homolog, GPR30, and occurs via trans-activation of the epidermal growth factor receptor through release of HB-EGF. Mol Endocrinol. 2000, 14: 1649-1660.CrossRefPubMed
40.
go back to reference Filardo EJ, Graeber CT, Quinn JA, Resnick MB, Giri D, DeLellis RA, Steinhoff MM, Sabo E: Distribution of GPR30, a seven membrane-spanning estrogen receptor, in primary breast cancer and its association with clinicopathologic determinants of tumor progression. Clin Cancer Res. 2006, 12: 6359-6366.CrossRefPubMed Filardo EJ, Graeber CT, Quinn JA, Resnick MB, Giri D, DeLellis RA, Steinhoff MM, Sabo E: Distribution of GPR30, a seven membrane-spanning estrogen receptor, in primary breast cancer and its association with clinicopathologic determinants of tumor progression. Clin Cancer Res. 2006, 12: 6359-6366.CrossRefPubMed
41.
go back to reference Prossnitz ER, Arterburn JB, Smith HO, Oprea TI, Sklar LA, Hathaway HJ: Estrogen signaling through the transmembrane G protein-coupled receptor GPR30. Annu Rev Physiol. 2008, 70: 165-190.CrossRefPubMed Prossnitz ER, Arterburn JB, Smith HO, Oprea TI, Sklar LA, Hathaway HJ: Estrogen signaling through the transmembrane G protein-coupled receptor GPR30. Annu Rev Physiol. 2008, 70: 165-190.CrossRefPubMed
44.
go back to reference Ariazi EA, Brailoiu E, Yerrum S, Shupp HA, Slifker MJ, Cunliffe HE, Black MA, Donato AL, Arterburn JB, Oprea TI, et al: The G Protein–Coupled Receptor GPR30 Inhibits Proliferation of Estrogen Receptor–Positive Breast Cancer Cells. Cancer Res. 2010, 70: 1184-1194.CrossRefPubMedPubMedCentral Ariazi EA, Brailoiu E, Yerrum S, Shupp HA, Slifker MJ, Cunliffe HE, Black MA, Donato AL, Arterburn JB, Oprea TI, et al: The G Protein–Coupled Receptor GPR30 Inhibits Proliferation of Estrogen Receptor–Positive Breast Cancer Cells. Cancer Res. 2010, 70: 1184-1194.CrossRefPubMedPubMedCentral
45.
go back to reference Langer G, Bader B, Meoli L, Isensee J, Delbeck M, Noppinger PR, Otto C: A critical review of fundamental controversies in the field of GPR30 research. Steroids. 2010, 75: 603-610.CrossRefPubMed Langer G, Bader B, Meoli L, Isensee J, Delbeck M, Noppinger PR, Otto C: A critical review of fundamental controversies in the field of GPR30 research. Steroids. 2010, 75: 603-610.CrossRefPubMed
46.
go back to reference Barton M: Position paper: The membrane estrogen receptor GPER/GPR30: Clues and questions. Steroids. 2012, 77: 935-942.CrossRefPubMed Barton M: Position paper: The membrane estrogen receptor GPER/GPR30: Clues and questions. Steroids. 2012, 77: 935-942.CrossRefPubMed
47.
go back to reference Carmeci C, Thompson DA, Ring HZ, Francke U, Weigel RJ: Identification of a gene (GPR30) with homology to the G-protein-coupled receptor superfamily associated with estrogen receptor expression in breast cancer. Genomics. 1997, 45: 607-617.CrossRefPubMed Carmeci C, Thompson DA, Ring HZ, Francke U, Weigel RJ: Identification of a gene (GPR30) with homology to the G-protein-coupled receptor superfamily associated with estrogen receptor expression in breast cancer. Genomics. 1997, 45: 607-617.CrossRefPubMed
48.
go back to reference Feng Y, Gregor P: Cloning of a Novel Member of the G Protein-Coupled Receptor Family Related to Peptide Receptors. Biochem Biophys Res Commun. 1997, 231: 651-654.CrossRefPubMed Feng Y, Gregor P: Cloning of a Novel Member of the G Protein-Coupled Receptor Family Related to Peptide Receptors. Biochem Biophys Res Commun. 1997, 231: 651-654.CrossRefPubMed
49.
go back to reference Ramirez RD, Sheridan S, Girard L, Sato M, Kim Y, Pollack J, Peyton M, Zou Y, Kurie JM, Dimaio JM, et al: Immortalization of human bronchial epithelial cells in the absence of viral oncoproteins. Cancer Res. 2004, 64: 9027-9034.CrossRefPubMed Ramirez RD, Sheridan S, Girard L, Sato M, Kim Y, Pollack J, Peyton M, Zou Y, Kurie JM, Dimaio JM, et al: Immortalization of human bronchial epithelial cells in the absence of viral oncoproteins. Cancer Res. 2004, 64: 9027-9034.CrossRefPubMed
50.
go back to reference Masuda A, Kondo M, Saito T, Yatabe Y, Kobayashi T, Okamoto M, Suyama M, Takahashi T, Takahashi T: Establishment of Human Peripheral Lung Epithelial Cell Lines (HPL1) Retaining Differentiated Characteristics and Responsiveness to Epidermal Growth Factor, Hepatocyte Growth Factor, and Transforming Growth Factor β1. Cancer Res. 1997, 57: 4898-4904.PubMed Masuda A, Kondo M, Saito T, Yatabe Y, Kobayashi T, Okamoto M, Suyama M, Takahashi T, Takahashi T: Establishment of Human Peripheral Lung Epithelial Cell Lines (HPL1) Retaining Differentiated Characteristics and Responsiveness to Epidermal Growth Factor, Hepatocyte Growth Factor, and Transforming Growth Factor β1. Cancer Res. 1997, 57: 4898-4904.PubMed
51.
go back to reference Al-Wadei HAN, Al-Wadei MH, Masi T, Schuller HM: Chronic exposure to estrogen and the tobacco carcinogen NNK cooperatively modulates nicotinic receptors in small airway epithelial cells. Lung Cancer. 2010, 69: 33-39.CrossRefPubMed Al-Wadei HAN, Al-Wadei MH, Masi T, Schuller HM: Chronic exposure to estrogen and the tobacco carcinogen NNK cooperatively modulates nicotinic receptors in small airway epithelial cells. Lung Cancer. 2010, 69: 33-39.CrossRefPubMed
52.
go back to reference Schuller HM, Al-Wadei HAN, Majidi M: Gamma-aminobutyric acid, a potential tumor suppressor for small airway-derived lung adenocarcinoma. Carcinogenesis. 2008, 29: 1979-1985.CrossRefPubMedPubMedCentral Schuller HM, Al-Wadei HAN, Majidi M: Gamma-aminobutyric acid, a potential tumor suppressor for small airway-derived lung adenocarcinoma. Carcinogenesis. 2008, 29: 1979-1985.CrossRefPubMedPubMedCentral
53.
go back to reference Maiti K, Paul JW, Read M, Chan EC, Riley SC, Nahar P, Smith R: G-1-Activated Membrane Estrogen Receptors Mediate Increased Contractility of the Human Myometrium. Endocrinology. 2011, 152: 2448-2455.CrossRefPubMed Maiti K, Paul JW, Read M, Chan EC, Riley SC, Nahar P, Smith R: G-1-Activated Membrane Estrogen Receptors Mediate Increased Contractility of the Human Myometrium. Endocrinology. 2011, 152: 2448-2455.CrossRefPubMed
54.
go back to reference Milligan G, Canals M, Pediani JD, Ellis J, Lopez-Gimenez JF: The role of GPCR dimerisation/oligomerisation in receptor signalling. Ernst Schering Found Symp Proc. 2006, 2006: 145-161. Milligan G, Canals M, Pediani JD, Ellis J, Lopez-Gimenez JF: The role of GPCR dimerisation/oligomerisation in receptor signalling. Ernst Schering Found Symp Proc. 2006, 2006: 145-161.
55.
go back to reference Rios CD, Jordan BA, Gomes I, Devi LA: G-protein-coupled receptor dimerization: modulation of receptor function. Pharmacology & Therapeutics. 2001, 92: 71-87.CrossRef Rios CD, Jordan BA, Gomes I, Devi LA: G-protein-coupled receptor dimerization: modulation of receptor function. Pharmacology & Therapeutics. 2001, 92: 71-87.CrossRef
56.
go back to reference Sandén C, Broselid S, Cornmark L, Andersson K, Daszkiewicz-Nilsson J, Mårtensson UEA, Olde B, Leeb-Lundberg LMF: G Protein-Coupled Estrogen Receptor 1/G Protein-Coupled Receptor 30 Localizes in the Plasma Membrane and Traffics Intracellularly on Cytokeratin Intermediate Filaments. Mol Pharmacol. 2011, 79: 400-410.CrossRefPubMed Sandén C, Broselid S, Cornmark L, Andersson K, Daszkiewicz-Nilsson J, Mårtensson UEA, Olde B, Leeb-Lundberg LMF: G Protein-Coupled Estrogen Receptor 1/G Protein-Coupled Receptor 30 Localizes in the Plasma Membrane and Traffics Intracellularly on Cytokeratin Intermediate Filaments. Mol Pharmacol. 2011, 79: 400-410.CrossRefPubMed
57.
go back to reference Giess M, Lattrich C, Springwald A, Goerse R, Ortmann O, Treeck O: GPR30 gene polymorphisms are associated with progesterone receptor status and histopathological characteristics of breast cancer patients. The Journal of steroid biochemistry and molecular biology. 2010, 118: 7-12.CrossRefPubMed Giess M, Lattrich C, Springwald A, Goerse R, Ortmann O, Treeck O: GPR30 gene polymorphisms are associated with progesterone receptor status and histopathological characteristics of breast cancer patients. The Journal of steroid biochemistry and molecular biology. 2010, 118: 7-12.CrossRefPubMed
58.
go back to reference Prossnitz ER, Barton M: The G-protein-coupled estrogen receptor GPER in health and disease. 2011, Endocrinology: Nature reviews Prossnitz ER, Barton M: The G-protein-coupled estrogen receptor GPER in health and disease. 2011, Endocrinology: Nature reviews
59.
go back to reference Tu G, Hu D, Yang G, Yu T: The correlation between GPR30 and clinicopathologic variables in breast carcinomas. Technol Cancer Res Treat. 2009, 8: 231-234.CrossRefPubMed Tu G, Hu D, Yang G, Yu T: The correlation between GPR30 and clinicopathologic variables in breast carcinomas. Technol Cancer Res Treat. 2009, 8: 231-234.CrossRefPubMed
60.
go back to reference Smith HO, Leslie KK, Singh M, Qualls CR, Revankar CM, Joste NE, Prossnitz ER: GPR30: a novel indicator of poor survival for endometrial carcinoma. Am J Obstet Gynecol. 2007, 196 (386): e381-e389. discussion 386 e389-311 Smith HO, Leslie KK, Singh M, Qualls CR, Revankar CM, Joste NE, Prossnitz ER: GPR30: a novel indicator of poor survival for endometrial carcinoma. Am J Obstet Gynecol. 2007, 196 (386): e381-e389. discussion 386 e389-311
61.
go back to reference Vivacqua A, Bonofiglio D, Recchia AG, Musti AM, Picard D, Ando S, Maggiolini M: The G protein-coupled receptor GPR30 mediates the proliferative effects induced by 17beta-estradiol and hydroxytamoxifen in endometrial cancer cells. Mol Endocrinol. 2006, 20: 631-646.CrossRefPubMed Vivacqua A, Bonofiglio D, Recchia AG, Musti AM, Picard D, Ando S, Maggiolini M: The G protein-coupled receptor GPR30 mediates the proliferative effects induced by 17beta-estradiol and hydroxytamoxifen in endometrial cancer cells. Mol Endocrinol. 2006, 20: 631-646.CrossRefPubMed
62.
go back to reference Smith HO, Arias-Pulido H, Kuo DY, Howard T, Qualls CR, Lee SJ, Verschraegen CF, Hathaway HJ, Joste NE, Prossnitz ER: GPR30 predicts poor survival for ovarian cancer. Gynecol Oncol. 2009, 114: 465-471.CrossRefPubMedPubMedCentral Smith HO, Arias-Pulido H, Kuo DY, Howard T, Qualls CR, Lee SJ, Verschraegen CF, Hathaway HJ, Joste NE, Prossnitz ER: GPR30 predicts poor survival for ovarian cancer. Gynecol Oncol. 2009, 114: 465-471.CrossRefPubMedPubMedCentral
63.
go back to reference Vivacqua A, Bonofiglio D, Albanito L, Madeo A, Rago V, Carpino A, Musti AM, Picard D, Ando S, Maggiolini M: 17beta-estradiol, genistein, and 4-hydroxytamoxifen induce the proliferation of thyroid cancer cells through the g protein-coupled receptor GPR30. Mol Pharmacol. 2006, 70: 1414-1423.CrossRefPubMed Vivacqua A, Bonofiglio D, Albanito L, Madeo A, Rago V, Carpino A, Musti AM, Picard D, Ando S, Maggiolini M: 17beta-estradiol, genistein, and 4-hydroxytamoxifen induce the proliferation of thyroid cancer cells through the g protein-coupled receptor GPR30. Mol Pharmacol. 2006, 70: 1414-1423.CrossRefPubMed
64.
go back to reference Luo HJ, Luo P, Yang GL, Peng QL, Liu MR, Tu G: G-protein Coupled Estrogen Receptor 1 Expression in Primary Breast Cancers and Its Correlation with Clinicopathological Variables. J Breast Cancer. 2011, 14: 185-190.CrossRefPubMedPubMedCentral Luo HJ, Luo P, Yang GL, Peng QL, Liu MR, Tu G: G-protein Coupled Estrogen Receptor 1 Expression in Primary Breast Cancers and Its Correlation with Clinicopathological Variables. J Breast Cancer. 2011, 14: 185-190.CrossRefPubMedPubMedCentral
65.
go back to reference Arias-Pulido H, Royce M, Gong Y, Joste N, Lomo L, Lee SJ, Chaher N, Verschraegen C, Lara J, Prossnitz ER, Cristofanilli M: GPR30 and estrogen receptor expression: new insights into hormone dependence of inflammatory breast cancer. Breast Cancer Res Treat. 2010, 123: 51-58.CrossRefPubMed Arias-Pulido H, Royce M, Gong Y, Joste N, Lomo L, Lee SJ, Chaher N, Verschraegen C, Lara J, Prossnitz ER, Cristofanilli M: GPR30 and estrogen receptor expression: new insights into hormone dependence of inflammatory breast cancer. Breast Cancer Res Treat. 2010, 123: 51-58.CrossRefPubMed
66.
go back to reference Krakstad C, Trovik J, Wik E, Engelsen IB, Werner HM, Birkeland E, Raeder MB, Oyan AM, Stefansson IM, Kalland KH, et al: Loss of GPER identifies new targets for therapy among a subgroup of ERalpha-positive endometrial cancer patients with poor outcome. Br J Cancer. 2012, 106: 1682-1688.CrossRefPubMedPubMedCentral Krakstad C, Trovik J, Wik E, Engelsen IB, Werner HM, Birkeland E, Raeder MB, Oyan AM, Stefansson IM, Kalland KH, et al: Loss of GPER identifies new targets for therapy among a subgroup of ERalpha-positive endometrial cancer patients with poor outcome. Br J Cancer. 2012, 106: 1682-1688.CrossRefPubMedPubMedCentral
67.
go back to reference Gao F, Ma X, Ostmann AB, Das SK: GPR30 Activation Opposes Estrogen-Dependent Uterine Growth via Inhibition of Stromal ERK1/2 and Estrogen Receptor Alpha (ERα) Phosphorylation Signals. Endocrinology. 2011, 152: 1434-1447.CrossRefPubMedPubMedCentral Gao F, Ma X, Ostmann AB, Das SK: GPR30 Activation Opposes Estrogen-Dependent Uterine Growth via Inhibition of Stromal ERK1/2 and Estrogen Receptor Alpha (ERα) Phosphorylation Signals. Endocrinology. 2011, 152: 1434-1447.CrossRefPubMedPubMedCentral
68.
go back to reference Fasco MJ, Hurteau GJ, Spivack SD: Gender-dependent expression of alpha and beta estrogen receptors in human nontumor and tumor lung tissue. Mol Cell Endocrinol. 2002, 188: 125-140.CrossRefPubMed Fasco MJ, Hurteau GJ, Spivack SD: Gender-dependent expression of alpha and beta estrogen receptors in human nontumor and tumor lung tissue. Mol Cell Endocrinol. 2002, 188: 125-140.CrossRefPubMed
69.
go back to reference Stabile LP, Siegfried JM: Sex and gender differences in lung cancer. J Gend Specif Med. 2003, 6: 37-48.PubMed Stabile LP, Siegfried JM: Sex and gender differences in lung cancer. J Gend Specif Med. 2003, 6: 37-48.PubMed
71.
go back to reference Otto C, Rohde-Schulz B, Schwarz G, Fuchs I, Klewer M, Brittain D, Langer G, Bader B, Prelle K, Nubbemeyer R, Fritzemeier KH: G protein-coupled receptor 30 localizes to the endoplasmic reticulum and is not activated by estradiol. Endocrinology. 2008, 149: 4846-4856.CrossRefPubMed Otto C, Rohde-Schulz B, Schwarz G, Fuchs I, Klewer M, Brittain D, Langer G, Bader B, Prelle K, Nubbemeyer R, Fritzemeier KH: G protein-coupled receptor 30 localizes to the endoplasmic reticulum and is not activated by estradiol. Endocrinology. 2008, 149: 4846-4856.CrossRefPubMed
72.
go back to reference Kang L, Zhang X, Xie Y, Tu Y, Wang D, Liu Z, Wang ZY: Involvement of estrogen receptor variant ER-alpha36, not GPR30, in nongenomic estrogen signaling. Mol Endocrinol. 2010, 24: 709-721.CrossRefPubMedPubMedCentral Kang L, Zhang X, Xie Y, Tu Y, Wang D, Liu Z, Wang ZY: Involvement of estrogen receptor variant ER-alpha36, not GPR30, in nongenomic estrogen signaling. Mol Endocrinol. 2010, 24: 709-721.CrossRefPubMedPubMedCentral
73.
go back to reference Otto C, Fuchs I, Kauselmann G, Kern H, Zevnik B, Andreasen P, Schwarz G, Altmann H, Klewer M, Schoor M, et al: GPR30 does not mediate estrogenic responses in reproductive organs in mice. Biol Reprod. 2009, 80: 34-41.CrossRefPubMed Otto C, Fuchs I, Kauselmann G, Kern H, Zevnik B, Andreasen P, Schwarz G, Altmann H, Klewer M, Schoor M, et al: GPR30 does not mediate estrogenic responses in reproductive organs in mice. Biol Reprod. 2009, 80: 34-41.CrossRefPubMed
74.
go back to reference Ahola TM, Alkio N, Manninen T, Ylikomi T: Progestin and G protein-coupled receptor 30 inhibit mitogen-activated protein kinase activity in MCF-7 breast cancer cells. Endocrinology. 2002, 143: 4620-4626.CrossRefPubMed Ahola TM, Alkio N, Manninen T, Ylikomi T: Progestin and G protein-coupled receptor 30 inhibit mitogen-activated protein kinase activity in MCF-7 breast cancer cells. Endocrinology. 2002, 143: 4620-4626.CrossRefPubMed
75.
go back to reference Ahola TM, Manninen T, Alkio N, Ylikomi T: G protein-coupled receptor 30 is critical for a progestin-induced growth inhibition in MCF-7 breast cancer cells. Endocrinology. 2002, 143: 3376-3384.CrossRefPubMed Ahola TM, Manninen T, Alkio N, Ylikomi T: G protein-coupled receptor 30 is critical for a progestin-induced growth inhibition in MCF-7 breast cancer cells. Endocrinology. 2002, 143: 3376-3384.CrossRefPubMed
76.
go back to reference Ahola TM, Purmonen S, Pennanen P, Zhuang YH, Tuohimaa P, Ylikomi T: Progestin upregulates G-protein-coupled receptor 30 in breast cancer cells. Eur J Biochem. 2002, 269: 2485-2490.CrossRefPubMed Ahola TM, Purmonen S, Pennanen P, Zhuang YH, Tuohimaa P, Ylikomi T: Progestin upregulates G-protein-coupled receptor 30 in breast cancer cells. Eur J Biochem. 2002, 269: 2485-2490.CrossRefPubMed
77.
go back to reference Albanito L, Madeo A, Lappano R, Vivacqua A, Rago V, Carpino A, Oprea TI, Prossnitz ER, Musti AM, Ando S, Maggiolini M: G Protein-Coupled Receptor 30 (GPR30) Mediates Gene Expression Changes and Growth Response to 17{beta}-Estradiol and Selective GPR30 Ligand G-1 in Ovarian Cancer Cells. Cancer Res. 2007, 67: 1859-1866.CrossRefPubMed Albanito L, Madeo A, Lappano R, Vivacqua A, Rago V, Carpino A, Oprea TI, Prossnitz ER, Musti AM, Ando S, Maggiolini M: G Protein-Coupled Receptor 30 (GPR30) Mediates Gene Expression Changes and Growth Response to 17{beta}-Estradiol and Selective GPR30 Ligand G-1 in Ovarian Cancer Cells. Cancer Res. 2007, 67: 1859-1866.CrossRefPubMed
78.
go back to reference Thomas P, Pang Y, Filardo EJ, Dong J: Identity of an Estrogen Membrane Receptor Coupled to a G Protein in Human Breast Cancer Cells. Endocrinology. 2005, 146: 624-632.CrossRefPubMed Thomas P, Pang Y, Filardo EJ, Dong J: Identity of an Estrogen Membrane Receptor Coupled to a G Protein in Human Breast Cancer Cells. Endocrinology. 2005, 146: 624-632.CrossRefPubMed
79.
go back to reference Giovannetti E, Erdem L, Olcay E, Leon LG, Peters GJ: Influence of polymorphisms on EGFR targeted therapy in non-small-cell lung cancer. Front Biosci. 2011, 16: 116-130.CrossRef Giovannetti E, Erdem L, Olcay E, Leon LG, Peters GJ: Influence of polymorphisms on EGFR targeted therapy in non-small-cell lung cancer. Front Biosci. 2011, 16: 116-130.CrossRef
80.
go back to reference Keedy VL, Temin S, Somerfield MR, Beasley MB, Johnson DH, McShane LM, Milton DT, Strawn JR, Wakelee HA, Giaccone G: American Society of Clinical Oncology Provisional Clinical Opinion: Epidermal Growth Factor Receptor (EGFR) Mutation Testing for Patients With Advanced Non–Small-Cell Lung Cancer Considering First-Line EGFR Tyrosine Kinase Inhibitor Therapy. J Clin Oncol. 2011 Keedy VL, Temin S, Somerfield MR, Beasley MB, Johnson DH, McShane LM, Milton DT, Strawn JR, Wakelee HA, Giaccone G: American Society of Clinical Oncology Provisional Clinical Opinion: Epidermal Growth Factor Receptor (EGFR) Mutation Testing for Patients With Advanced Non–Small-Cell Lung Cancer Considering First-Line EGFR Tyrosine Kinase Inhibitor Therapy. J Clin Oncol. 2011
81.
go back to reference Girgert R, Emons G, Grundker C: Inactivation of GPR30 reduces growth of triple-negative breast cancer cells: possible application in targeted therapy. Breast Cancer Res Treat. 2012, 134: 199-205.CrossRefPubMedPubMedCentral Girgert R, Emons G, Grundker C: Inactivation of GPR30 reduces growth of triple-negative breast cancer cells: possible application in targeted therapy. Breast Cancer Res Treat. 2012, 134: 199-205.CrossRefPubMedPubMedCentral
Metadata
Title
Enhanced expression of G-protein coupled estrogen receptor (GPER/GPR30) in lung cancer
Authors
Venkatakrishna Rao Jala
Brandie N Radde
Bodduluri Haribabu
Carolyn M Klinge
Publication date
01-12-2012
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2012
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-12-624

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