Skip to main content
Top
Published in: Breast Cancer Research 6/2007

Open Access 01-12-2007 | Research article

Regulator of G-protein signalling 2 mRNA is differentially expressed in mammary epithelial subpopulations and over-expressed in the majority of breast cancers

Authors: Matthew J Smalley, Marjan Iravani, Maria Leao, Anita Grigoriadis, Howard Kendrick, Tim Dexter, Kerry Fenwick, Joseph L Regan, Kara Britt, Sarah McDonald, Christopher J Lord, Alan MacKay, Alan Ashworth

Published in: Breast Cancer Research | Issue 6/2007

Login to get access

Abstract

Introduction

To understand which signalling pathways become deregulated in breast cancer, it is necessary to identify functionally significant gene expression patterns in the stem, progenitor, transit amplifying and differentiated cells of the mammary epithelium. We have previously used the markers 33A10, CD24 and Sca-1 to identify mouse mammary epithelial cell subpopulations. We now investigate the relationship between cells expressing these markers and use gene expression microarray analysis to identify genes differentially expressed in the cell populations.

Methods

Freshly isolated primary mouse mammary epithelial cells were separated on the basis of staining with the 33A10 antibody and an α-Sca-1 antibody. The populations identified were profiled using gene expression microarray analysis. Gene expression patterns were confirmed on normal mouse and human mammary epithelial subpopulations and were examined in a panel of breast cancer samples and cell lines.

Results

Analysis of the separated populations demonstrated that Sca-1- 33A10High stained cells were estrogen receptor α (Esr1)- luminal epithelial cells, whereas Sca-1+ 33A10Low/- stained cells were a mix of nonepithelial cells and Esr1+ epithelial cells. Analysis of the gene expression data identified the gene Rgs2 (regulator of G-protein signalling 2) as being highly expressed in the Sca-1- 33A10Low/- population, which included myoepithelial/basal cells. RGS2 has previously been described as a regulator of angiotensin II receptor signalling. Gene expression analysis by quantitative real-time RT-PCR of cells separated on the basis of CD24 and Sca-1 expression confirmed that Rgs2 was more highly expressed in mouse myoepithelial/basal mammary cells than luminal cells. This expression pattern was conserved in normal human breast cells. Functional analysis demonstrated RGS2 to be a modulator of oxytocin receptor signalling. The potential significance of RGS2 expression in breast cancer was demonstrated by semi-quantitative RT-PCR analysis, data mining and quantitative real-time RT-PCR approaches, which showed that RGS2 was expressed in the majority of solid breast cancers at much higher levels than in normal human mammary cells.

Conclusion

Molecular analysis of prospectively isolated mammary epithelial cells identified RGS2 as a modulator of oxytocin receptor signalling, which is highly expressed in the myoepithelial cells. The RGS2 gene, but not the oxytocin receptor, was also shown to be over-expressed in the majority of breast cancers, identifying the product of this gene, or the pathway(s) it regulates, as potentially significant therapeutic targets.
Appendix
Available only for authorised users
Literature
1.
go back to reference Ali S, Coombes RC: Endocrine-responsive breast cancer and strategies for combating resistance. Nat Rev Cancer. 2002, 2: 101-112. 10.1038/nrc721.CrossRefPubMed Ali S, Coombes RC: Endocrine-responsive breast cancer and strategies for combating resistance. Nat Rev Cancer. 2002, 2: 101-112. 10.1038/nrc721.CrossRefPubMed
2.
go back to reference Goffin V, Bernichtein S, Touraine P, Kelly PA: Development and potential clinical uses of human prolactin receptor antagonists. Endocr Rev. 2005, 26: 400-422. 10.1210/er.2004-0016.CrossRefPubMed Goffin V, Bernichtein S, Touraine P, Kelly PA: Development and potential clinical uses of human prolactin receptor antagonists. Endocr Rev. 2005, 26: 400-422. 10.1210/er.2004-0016.CrossRefPubMed
3.
go back to reference Stern DF: ErbBs in mammary development. Exp Cell Res. 2003, 284: 89-98. 10.1016/S0014-4827(02)00103-9.CrossRefPubMed Stern DF: ErbBs in mammary development. Exp Cell Res. 2003, 284: 89-98. 10.1016/S0014-4827(02)00103-9.CrossRefPubMed
4.
go back to reference Zingg HH, Laporte SA: The oxytocin receptor. Trends Endocrinol Metab. 2003, 14: 222-227. 10.1016/S1043-2760(03)00080-8.CrossRefPubMed Zingg HH, Laporte SA: The oxytocin receptor. Trends Endocrinol Metab. 2003, 14: 222-227. 10.1016/S1043-2760(03)00080-8.CrossRefPubMed
5.
go back to reference Cassoni P, Sapino A, Marrocco T, Chini B, Bussolati G: Oxytocin and oxytocin receptors in cancer cells and proliferation. J Neuroendocrinol. 2004, 16: 362-364. 10.1111/j.0953-8194.2004.01165.x.CrossRefPubMed Cassoni P, Sapino A, Marrocco T, Chini B, Bussolati G: Oxytocin and oxytocin receptors in cancer cells and proliferation. J Neuroendocrinol. 2004, 16: 362-364. 10.1111/j.0953-8194.2004.01165.x.CrossRefPubMed
6.
go back to reference Ito Y, Kobayashi T, Kimura T, Matsuura N, Wakasugi E, Takeda T, Shimano T, Kubota Y, Nobunaga T, Makino Y, et al: Investigation of the oxytocin receptor expression in human breast cancer tissue using newly established monoclonal antibodies. Endocrinology. 1996, 137: 773-779. 10.1210/en.137.2.773.CrossRefPubMed Ito Y, Kobayashi T, Kimura T, Matsuura N, Wakasugi E, Takeda T, Shimano T, Kubota Y, Nobunaga T, Makino Y, et al: Investigation of the oxytocin receptor expression in human breast cancer tissue using newly established monoclonal antibodies. Endocrinology. 1996, 137: 773-779. 10.1210/en.137.2.773.CrossRefPubMed
7.
go back to reference Bussolati G, Cassoni P, Ghisolfi G, Negro F, Sapino A: Immunolocalization and gene expression of oxytocin receptors in carcinomas and non-neoplastic tissues of the breast. Am J Pathol. 1996, 148: 1895-1903.PubMedPubMedCentral Bussolati G, Cassoni P, Ghisolfi G, Negro F, Sapino A: Immunolocalization and gene expression of oxytocin receptors in carcinomas and non-neoplastic tissues of the breast. Am J Pathol. 1996, 148: 1895-1903.PubMedPubMedCentral
8.
go back to reference Anderson E, Clarke RB, Howell A: Estrogen responsiveness and control of normal human breast proliferation. J Mammary Gland Biol Neoplasia. 1998, 3: 23-35. 10.1023/A:1018718117113.CrossRefPubMed Anderson E, Clarke RB, Howell A: Estrogen responsiveness and control of normal human breast proliferation. J Mammary Gland Biol Neoplasia. 1998, 3: 23-35. 10.1023/A:1018718117113.CrossRefPubMed
9.
go back to reference Kelly PA, Bachelot A, Kedzia C, Hennighausen L, Ormandy CJ, Kopchick JJ, Binart N: The role of prolactin and growth hormone in mammary gland development. Mol Cell Endocrinol. 2002, 197: 127-131. 10.1016/S0303-7207(02)00286-1.CrossRefPubMed Kelly PA, Bachelot A, Kedzia C, Hennighausen L, Ormandy CJ, Kopchick JJ, Binart N: The role of prolactin and growth hormone in mammary gland development. Mol Cell Endocrinol. 2002, 197: 127-131. 10.1016/S0303-7207(02)00286-1.CrossRefPubMed
10.
go back to reference Smalley M, Ashworth A: Stem cells and breast cancer: a field in transit. Nat Rev Cancer. 2003, 3: 832-844. 10.1038/nrc1212.CrossRefPubMed Smalley M, Ashworth A: Stem cells and breast cancer: a field in transit. Nat Rev Cancer. 2003, 3: 832-844. 10.1038/nrc1212.CrossRefPubMed
11.
go back to reference Shackleton M, Vaillant F, Simpson KJ, Stingl J, Smyth GK, Asselin-Labat ML, Wu L, Lindeman GJ, Visvader JE: Generation of a functional mammary gland from a single stem cell. Nature. 2006, 439: 84-88. 10.1038/nature04372.CrossRefPubMed Shackleton M, Vaillant F, Simpson KJ, Stingl J, Smyth GK, Asselin-Labat ML, Wu L, Lindeman GJ, Visvader JE: Generation of a functional mammary gland from a single stem cell. Nature. 2006, 439: 84-88. 10.1038/nature04372.CrossRefPubMed
12.
go back to reference Sleeman KE, Kendrick H, Ashworth A, Isacke CM, Smalley MJ: CD24 staining of mouse mammary gland cells defines luminal epithelial, myoepithelial/basal and non-epithelial cells. Breast Cancer Res. 2006, 8: R7-10.1186/bcr1371.CrossRefPubMed Sleeman KE, Kendrick H, Ashworth A, Isacke CM, Smalley MJ: CD24 staining of mouse mammary gland cells defines luminal epithelial, myoepithelial/basal and non-epithelial cells. Breast Cancer Res. 2006, 8: R7-10.1186/bcr1371.CrossRefPubMed
13.
go back to reference Stingl J, Eirew P, Ricketson I, Shackleton M, Vaillant F, Choi D, Li HI, Eaves CJ: Purification and unique properties of mammary epithelial stem cells. Nature. 2006, 439: 993-997.PubMed Stingl J, Eirew P, Ricketson I, Shackleton M, Vaillant F, Choi D, Li HI, Eaves CJ: Purification and unique properties of mammary epithelial stem cells. Nature. 2006, 439: 993-997.PubMed
14.
go back to reference Sleeman KE, Kendrick H, Robertson D, Isacke CM, Ashworth A, Smalley MJ: Dissociation of estrogen receptor expression and in vivo stem cell activity in the mammary gland. J Cell Biol. 2007, 176: 19-26. 10.1083/jcb.200604065.CrossRefPubMedPubMedCentral Sleeman KE, Kendrick H, Robertson D, Isacke CM, Ashworth A, Smalley MJ: Dissociation of estrogen receptor expression and in vivo stem cell activity in the mammary gland. J Cell Biol. 2007, 176: 19-26. 10.1083/jcb.200604065.CrossRefPubMedPubMedCentral
15.
go back to reference Sonnenberg A, Daams H, Van der Valk MA, Hilkens J, Hilgers J: Development of mouse mammary gland: identification of stages in differentiation of luminal and myoepithelial cells using monoclonal antibodies and polyvalent antiserum against keratin. J Histochem Cytochem. 1986, 34: 1037-1046.CrossRefPubMed Sonnenberg A, Daams H, Van der Valk MA, Hilkens J, Hilgers J: Development of mouse mammary gland: identification of stages in differentiation of luminal and myoepithelial cells using monoclonal antibodies and polyvalent antiserum against keratin. J Histochem Cytochem. 1986, 34: 1037-1046.CrossRefPubMed
16.
go back to reference Sonnenberg A, van Balen P, Hilgers J, Schuuring E, Nusse R: Oncogene expression during progression of mouse mammary tumor cells; activity of a proviral enhancer and the resulting expression of int-2 is influenced by the state of differentiation. Embo J. 1987, 6: 121-125.PubMedPubMedCentral Sonnenberg A, van Balen P, Hilgers J, Schuuring E, Nusse R: Oncogene expression during progression of mouse mammary tumor cells; activity of a proviral enhancer and the resulting expression of int-2 is influenced by the state of differentiation. Embo J. 1987, 6: 121-125.PubMedPubMedCentral
17.
go back to reference Smalley MJ, Titley J, O'Hare MJ: Clonal characterization of mouse mammary luminal epithelial and myoepithelial cells separated by fluorescence-activated cell sorting. In Vitro Cell Dev Biol Anim. 1998, 34: 711-721. 10.1007/s11626-998-0067-0.CrossRefPubMed Smalley MJ, Titley J, O'Hare MJ: Clonal characterization of mouse mammary luminal epithelial and myoepithelial cells separated by fluorescence-activated cell sorting. In Vitro Cell Dev Biol Anim. 1998, 34: 711-721. 10.1007/s11626-998-0067-0.CrossRefPubMed
18.
go back to reference Smalley MJ, Titley J, Paterson H, Perusinghe N, Clarke C, O'Hare MJ: Differentiation of separated mouse mammary luminal epithelial and myoepithelial cells cultured on EHS matrix analyzed by indirect immunofluorescence of cytoskeletal antigens. J Histochem Cytochem. 1999, 47: 1513-1524.CrossRefPubMed Smalley MJ, Titley J, Paterson H, Perusinghe N, Clarke C, O'Hare MJ: Differentiation of separated mouse mammary luminal epithelial and myoepithelial cells cultured on EHS matrix analyzed by indirect immunofluorescence of cytoskeletal antigens. J Histochem Cytochem. 1999, 47: 1513-1524.CrossRefPubMed
20.
go back to reference Kargul GJ, Dudekula DB, Qian Y, Lim MK, Jaradat SA, Tanaka TS, Carter MG, Ko MS: Verification and initial annotation of the NIA mouse 15 K cDNA clone set. Nat Genet. 2001, 28: 17-18. 10.1038/88206.PubMed Kargul GJ, Dudekula DB, Qian Y, Lim MK, Jaradat SA, Tanaka TS, Carter MG, Ko MS: Verification and initial annotation of the NIA mouse 15 K cDNA clone set. Nat Genet. 2001, 28: 17-18. 10.1038/88206.PubMed
21.
go back to reference Tanaka TS, Jaradat SA, Lim MK, Kargul GJ, Wang X, Grahovac MJ, Pantano S, Sano Y, Piao Y, Nagaraja R, et al: Genome-wide expression profiling of mid-gestation placenta and embryo using a 15,000 mouse developmental cDNA microarray. Proc Natl Acad Sci USA. 2000, 97: 9127-9132. 10.1073/pnas.97.16.9127.CrossRefPubMedPubMedCentral Tanaka TS, Jaradat SA, Lim MK, Kargul GJ, Wang X, Grahovac MJ, Pantano S, Sano Y, Piao Y, Nagaraja R, et al: Genome-wide expression profiling of mid-gestation placenta and embryo using a 15,000 mouse developmental cDNA microarray. Proc Natl Acad Sci USA. 2000, 97: 9127-9132. 10.1073/pnas.97.16.9127.CrossRefPubMedPubMedCentral
22.
go back to reference Yang YH, Dudoit S, Luu P, Lin DM, Peng V, Ngai J, Speed TP: Normalization for cDNA microarray data: a robust composite method addressing single and multiple slide systematic variation. Nucleic Acids Res. 2002, 30: e15-10.1093/nar/30.4.e15.CrossRefPubMedPubMedCentral Yang YH, Dudoit S, Luu P, Lin DM, Peng V, Ngai J, Speed TP: Normalization for cDNA microarray data: a robust composite method addressing single and multiple slide systematic variation. Nucleic Acids Res. 2002, 30: e15-10.1093/nar/30.4.e15.CrossRefPubMedPubMedCentral
23.
go back to reference Smyth GK: Linear models and empirical Bayes methods for assessing differential expression in microarray experiments. Stat Appl Genet Mol Biol. 2004, 3: article 3-CrossRef Smyth GK: Linear models and empirical Bayes methods for assessing differential expression in microarray experiments. Stat Appl Genet Mol Biol. 2004, 3: article 3-CrossRef
26.
go back to reference Hochberg Y, Benjamini Y: More powerful procedures for multiple significance testing. Stat Med. 1990, 9: 811-818. 10.1002/sim.4780090710.CrossRefPubMed Hochberg Y, Benjamini Y: More powerful procedures for multiple significance testing. Stat Med. 1990, 9: 811-818. 10.1002/sim.4780090710.CrossRefPubMed
27.
go back to reference Brazma A, Hingamp P, Quackenbush J, Sherlock G, Spellman P, Stoeckert C, Aach J, Ansorge W, Ball CA, Causton HC, et al: Minimum information about a microarray experiment (MIAME)-toward standards for microarray data. Nat Genet. 2001, 29: 365-371. 10.1038/ng1201-365.CrossRefPubMed Brazma A, Hingamp P, Quackenbush J, Sherlock G, Spellman P, Stoeckert C, Aach J, Ansorge W, Ball CA, Causton HC, et al: Minimum information about a microarray experiment (MIAME)-toward standards for microarray data. Nat Genet. 2001, 29: 365-371. 10.1038/ng1201-365.CrossRefPubMed
29.
go back to reference Grigoriadis A, Mackay A, Reis-Filho JS, Steele D, Iseli C, Stevenson BJ, Jongeneel CV, Valgeirsson H, Fenwick K, Iravani M, et al: Establishment of the epithelial-specific transcriptome of normal and malignant human breast cells based on MPSS and array expression data. Breast Cancer Res. 2006, 8: R56-10.1186/bcr1604.CrossRefPubMedPubMedCentral Grigoriadis A, Mackay A, Reis-Filho JS, Steele D, Iseli C, Stevenson BJ, Jongeneel CV, Valgeirsson H, Fenwick K, Iravani M, et al: Establishment of the epithelial-specific transcriptome of normal and malignant human breast cells based on MPSS and array expression data. Breast Cancer Res. 2006, 8: R56-10.1186/bcr1604.CrossRefPubMedPubMedCentral
30.
go back to reference Stamps AC, Davies SC, Burman J, O'Hare MJ: Analysis of proviral integration in human mammary epithelial cell lines immortalized by retroviral infection with a temperature-sensitive SV40 T-antigen construct. Int J Cancer. 1994, 57: 865-874. 10.1002/ijc.2910570616.CrossRefPubMed Stamps AC, Davies SC, Burman J, O'Hare MJ: Analysis of proviral integration in human mammary epithelial cell lines immortalized by retroviral infection with a temperature-sensitive SV40 T-antigen construct. Int J Cancer. 1994, 57: 865-874. 10.1002/ijc.2910570616.CrossRefPubMed
31.
go back to reference Krief P, Saint-Ruf C, Bracke M, Boucheix C, Billard C, Billard M, Cassingena R, Jasmin C, Mareel M, Azzarone B: Acquisition of tumorigenic potential in the human myoepithelial HBL100 cell line is associated with decreased expression of HLA class I, class II and integrin beta 3 and increased expression of c-myc. Int J Cancer. 1989, 43: 658-664. 10.1002/ijc.2910430420.CrossRefPubMed Krief P, Saint-Ruf C, Bracke M, Boucheix C, Billard C, Billard M, Cassingena R, Jasmin C, Mareel M, Azzarone B: Acquisition of tumorigenic potential in the human myoepithelial HBL100 cell line is associated with decreased expression of HLA class I, class II and integrin beta 3 and increased expression of c-myc. Int J Cancer. 1989, 43: 658-664. 10.1002/ijc.2910430420.CrossRefPubMed
32.
go back to reference O'Hare MJ, Bond J, Clarke C, Takeuchi Y, Atherton AJ, Berry C, Moody J, Silver AR, Davies DC, Alsop AE, et al: Conditional immortalization of freshly isolated human mammary fibroblasts and endothelial cells. Proc Natl Acad Sci USA. 2001, 98: 646-651. 10.1073/pnas.98.2.646.CrossRefPubMedPubMedCentral O'Hare MJ, Bond J, Clarke C, Takeuchi Y, Atherton AJ, Berry C, Moody J, Silver AR, Davies DC, Alsop AE, et al: Conditional immortalization of freshly isolated human mammary fibroblasts and endothelial cells. Proc Natl Acad Sci USA. 2001, 98: 646-651. 10.1073/pnas.98.2.646.CrossRefPubMedPubMedCentral
33.
go back to reference Neve RM, Chin K, Fridlyand J, Yeh J, Baehner FL, Fevr T, Clark L, Bayani N, Coppe JP, Tong F, et al: A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes. Cancer Cell. 2006, 10: 515-527. 10.1016/j.ccr.2006.10.008.CrossRefPubMedPubMedCentral Neve RM, Chin K, Fridlyand J, Yeh J, Baehner FL, Fevr T, Clark L, Bayani N, Coppe JP, Tong F, et al: A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes. Cancer Cell. 2006, 10: 515-527. 10.1016/j.ccr.2006.10.008.CrossRefPubMedPubMedCentral
34.
go back to reference Copland JA, Jeng YJ, Strakova Z, Ives KL, Hellmich MR, Soloff MS: Demonstration of functional oxytocin receptors in human breast Hs578T cells and their up-regulation through a protein kinase C-dependent pathway. Endocrinology. 1999, 140: 2258-2267. 10.1210/en.140.5.2258.CrossRefPubMed Copland JA, Jeng YJ, Strakova Z, Ives KL, Hellmich MR, Soloff MS: Demonstration of functional oxytocin receptors in human breast Hs578T cells and their up-regulation through a protein kinase C-dependent pathway. Endocrinology. 1999, 140: 2258-2267. 10.1210/en.140.5.2258.CrossRefPubMed
36.
go back to reference Rimoldi V, Reversi A, Taverna E, Rosa P, Francolini M, Cassoni P, Parenti M, Chini B: Oxytocin receptor elicits different EGFR/MAPK activation patterns depending on its localization in caveolin-1 enriched domains. Oncogene. 2003, 22: 6054-6060. 10.1038/sj.onc.1206612.CrossRefPubMed Rimoldi V, Reversi A, Taverna E, Rosa P, Francolini M, Cassoni P, Parenti M, Chini B: Oxytocin receptor elicits different EGFR/MAPK activation patterns depending on its localization in caveolin-1 enriched domains. Oncogene. 2003, 22: 6054-6060. 10.1038/sj.onc.1206612.CrossRefPubMed
37.
go back to reference Minta A, Kao JP, Tsien RY: Fluorescent indicators for cytosolic calcium based on rhodamine and fluorescein chromophores. J Biol Chem. 1989, 264: 8171-8178.PubMed Minta A, Kao JP, Tsien RY: Fluorescent indicators for cytosolic calcium based on rhodamine and fluorescein chromophores. J Biol Chem. 1989, 264: 8171-8178.PubMed
38.
go back to reference Kehrl JH, Sinnarajah S: RGS2: a multifunctional regulator of G-protein signaling. Int J Biochem Cell Biol. 2002, 34: 432-438. 10.1016/S1357-2725(01)00141-8.CrossRefPubMed Kehrl JH, Sinnarajah S: RGS2: a multifunctional regulator of G-protein signaling. Int J Biochem Cell Biol. 2002, 34: 432-438. 10.1016/S1357-2725(01)00141-8.CrossRefPubMed
39.
go back to reference Sanborn BM: Hormones and calcium: mechanisms controlling uterine smooth muscle contractile activity. The Litchfield Lecture. Exp Physiol. 2001, 86: 223-237. 10.1113/eph8602179.CrossRefPubMed Sanborn BM: Hormones and calcium: mechanisms controlling uterine smooth muscle contractile activity. The Litchfield Lecture. Exp Physiol. 2001, 86: 223-237. 10.1113/eph8602179.CrossRefPubMed
40.
go back to reference Oh P, Schnitzer JE: Segregation of heterotrimeric G proteins in cell surface microdomains. G(q) binds caveolin to concentrate in caveolae, whereas G(i) and G(s) target lipid rafts by default. Mol Biol Cell. 2001, 12: 685-698.CrossRefPubMedPubMedCentral Oh P, Schnitzer JE: Segregation of heterotrimeric G proteins in cell surface microdomains. G(q) binds caveolin to concentrate in caveolae, whereas G(i) and G(s) target lipid rafts by default. Mol Biol Cell. 2001, 12: 685-698.CrossRefPubMedPubMedCentral
41.
go back to reference Heximer SP, Knutsen RH, Sun X, Kaltenbronn KM, Rhee MH, Peng N, Oliveira-dos-Santos A, Penninger JM, Muslin AJ, Steinberg TH, et al: Hypertension and prolonged vasoconstrictor signaling in RGS2-deficient mice. J Clin Invest. 2003, 111: 445-452. 10.1172/JCI200315598.CrossRefPubMedPubMedCentral Heximer SP, Knutsen RH, Sun X, Kaltenbronn KM, Rhee MH, Peng N, Oliveira-dos-Santos A, Penninger JM, Muslin AJ, Steinberg TH, et al: Hypertension and prolonged vasoconstrictor signaling in RGS2-deficient mice. J Clin Invest. 2003, 111: 445-452. 10.1172/JCI200315598.CrossRefPubMedPubMedCentral
42.
go back to reference Dorsam RT, Gutkind JS: G-protein-coupled receptors and cancer. Nat Rev Cancer. 2007, 7: 79-94. 10.1038/nrc2069.CrossRefPubMed Dorsam RT, Gutkind JS: G-protein-coupled receptors and cancer. Nat Rev Cancer. 2007, 7: 79-94. 10.1038/nrc2069.CrossRefPubMed
43.
go back to reference Riddle EL, Schwartzman RA, Bond M, Insel PA: Multi-tasking RGS proteins in the heart: the next therapeutic target?. Circ Res. 2005, 96: 401-411. 10.1161/01.RES.0000158287.49872.4e.CrossRefPubMed Riddle EL, Schwartzman RA, Bond M, Insel PA: Multi-tasking RGS proteins in the heart: the next therapeutic target?. Circ Res. 2005, 96: 401-411. 10.1161/01.RES.0000158287.49872.4e.CrossRefPubMed
44.
go back to reference Oliveira-Dos-Santos AJ, Matsumoto G, Snow BE, Bai D, Houston FP, Whishaw IQ, Mariathasan S, Sasaki T, Wakeham A, Ohashi PS, et al: Regulation of T cell activation, anxiety, and male aggression by RGS2. Proc Natl Acad Sci USA. 2000, 97: 12272-12277. 10.1073/pnas.220414397.CrossRefPubMedPubMedCentral Oliveira-Dos-Santos AJ, Matsumoto G, Snow BE, Bai D, Houston FP, Whishaw IQ, Mariathasan S, Sasaki T, Wakeham A, Ohashi PS, et al: Regulation of T cell activation, anxiety, and male aggression by RGS2. Proc Natl Acad Sci USA. 2000, 97: 12272-12277. 10.1073/pnas.220414397.CrossRefPubMedPubMedCentral
45.
go back to reference Li S, Huang S, Peng SB: Overexpression of G protein-coupled receptors in cancer cells: involvement in tumor progression. Int J Oncol. 2005, 27: 1329-1339.PubMed Li S, Huang S, Peng SB: Overexpression of G protein-coupled receptors in cancer cells: involvement in tumor progression. Int J Oncol. 2005, 27: 1329-1339.PubMed
46.
go back to reference Radeff-Huang J, Seasholtz TM, Matteo RG, Brown JH: G protein mediated signaling pathways in lysophospholipid induced cell proliferation and survival. J Cell Biochem. 2004, 92: 949-966. 10.1002/jcb.20094.CrossRefPubMed Radeff-Huang J, Seasholtz TM, Matteo RG, Brown JH: G protein mediated signaling pathways in lysophospholipid induced cell proliferation and survival. J Cell Biochem. 2004, 92: 949-966. 10.1002/jcb.20094.CrossRefPubMed
47.
go back to reference Yowell CW, Daaka Y: G protein-coupled receptors provide survival signals in prostate cancer. Clin Prostate Cancer. 2002, 1: 177-181.CrossRefPubMed Yowell CW, Daaka Y: G protein-coupled receptors provide survival signals in prostate cancer. Clin Prostate Cancer. 2002, 1: 177-181.CrossRefPubMed
48.
go back to reference Kaelin WG: The concept of synthetic lethality in the context of anticancer therapy. Nat Rev Cancer. 2005, 5: 689-698. 10.1038/nrc1691.CrossRefPubMed Kaelin WG: The concept of synthetic lethality in the context of anticancer therapy. Nat Rev Cancer. 2005, 5: 689-698. 10.1038/nrc1691.CrossRefPubMed
49.
go back to reference Roberts PJ, Der CJ: Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer. Oncogene. 2007, 26: 3291-3310. 10.1038/sj.onc.1210422.CrossRefPubMed Roberts PJ, Der CJ: Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer. Oncogene. 2007, 26: 3291-3310. 10.1038/sj.onc.1210422.CrossRefPubMed
50.
go back to reference Alonso MA, Millan J: The role of lipid rafts in signalling and membrane trafficking in T lymphocytes. J Cell Sci. 2001, 114: 3957-3965.PubMed Alonso MA, Millan J: The role of lipid rafts in signalling and membrane trafficking in T lymphocytes. J Cell Sci. 2001, 114: 3957-3965.PubMed
51.
go back to reference Simons K, Toomre D: Lipid rafts and signal transduction. Nat Rev Mol Cell Biol. 2000, 1: 31-39. 10.1038/35036052.CrossRefPubMed Simons K, Toomre D: Lipid rafts and signal transduction. Nat Rev Mol Cell Biol. 2000, 1: 31-39. 10.1038/35036052.CrossRefPubMed
52.
go back to reference Kolch W, Calder M, Gilbert D: When kinases meet mathematics: the systems biology of MAPK signalling. FEBS Lett. 2005, 579: 1891-1895. 10.1016/j.febslet.2005.02.002.CrossRefPubMed Kolch W, Calder M, Gilbert D: When kinases meet mathematics: the systems biology of MAPK signalling. FEBS Lett. 2005, 579: 1891-1895. 10.1016/j.febslet.2005.02.002.CrossRefPubMed
53.
go back to reference Pouyssegur J, Volmat V, Lenormand P: Fidelity and spatio-temporal control in MAP kinase (ERKs) signalling. Biochem Pharmacol. 2002, 64: 755-763. 10.1016/S0006-2952(02)01135-8.CrossRefPubMed Pouyssegur J, Volmat V, Lenormand P: Fidelity and spatio-temporal control in MAP kinase (ERKs) signalling. Biochem Pharmacol. 2002, 64: 755-763. 10.1016/S0006-2952(02)01135-8.CrossRefPubMed
Metadata
Title
Regulator of G-protein signalling 2 mRNA is differentially expressed in mammary epithelial subpopulations and over-expressed in the majority of breast cancers
Authors
Matthew J Smalley
Marjan Iravani
Maria Leao
Anita Grigoriadis
Howard Kendrick
Tim Dexter
Kerry Fenwick
Joseph L Regan
Kara Britt
Sarah McDonald
Christopher J Lord
Alan MacKay
Alan Ashworth
Publication date
01-12-2007
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 6/2007
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr1834

Other articles of this Issue 6/2007

Breast Cancer Research 6/2007 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine