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Published in: Journal of Ovarian Research 1/2009

Open Access 01-12-2009 | Brief communication

Aberrant STYK1 expression in ovarian cancer tissues and cell lines

Authors: Kesmic A Jackson, Gabriela Oprea, Jeffrey Handy, K Sean Kimbro

Published in: Journal of Ovarian Research | Issue 1/2009

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Abstract

Background

Overexpression of STYK1, a putative serine/threonine and tyrosine receptor protein kinase has been shown to confer tumorigenicity and metastatic potential to normal cells injected into nude mice. Mutation of a tyrosine residue in the catalytic STYK1 domain attenuates the tumorigenic potential of tumor cells in vivo, collectively, suggesting an oncogenic role for STYK1.

Methods

To investigate the role of STYK1 expression in ovarian cancer, a panel of normal, benign, and ovarian cancer tissues was evaluated for STYK1 immunoreactivity using STYK1 antibodies. In addition, mRNA levels were measured by reverse transcription PCR and real-time PCR of estrogen receptors, GPR30 and STYK1 following treatment of ovarian cell lines with estrogen or G1, a GPR30 agonist, as well as western analysis.

Results

Our data showed higher expression of STYK1 in cancer tissues versus normal or benign. Only normal or benign, and one cancer tissue were STYK1-negative. Moreover, benign and ovarian cancer cell lines expressed STYK1 as determined by RT-PCR. Estradiol treatment of these cells resulted in up- and down-regulation of STYK1 despite estrogen receptor status; whereas G-1, a GPR30-specific agonist, increased STYK1 mRNA levels higher than that of estradiol.

Conclusion

We conclude that STYK1 is expressed in ovarian cancer and is regulated by estrogen through a GPR30 hormone-signaling pathway, to the exclusion of estrogen receptor-alpha.
Appendix
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Literature
1.
go back to reference Lingeman CH: Etiology of cancer of the human ovary: a review. J Natl Cancer Inst 1974, 53: 1603–1618.PubMed Lingeman CH: Etiology of cancer of the human ovary: a review. J Natl Cancer Inst 1974, 53: 1603–1618.PubMed
2.
go back to reference Scott M, McCluggage WG, Hillan KJ, Hall PA, Russell SE: Altered patterns of transcription of the septin gene, SEPT9, in ovarian tumorigenesis. Int J Cancer 2006, 118: 1325–1329. 10.1002/ijc.21486PubMedCrossRef Scott M, McCluggage WG, Hillan KJ, Hall PA, Russell SE: Altered patterns of transcription of the septin gene, SEPT9, in ovarian tumorigenesis. Int J Cancer 2006, 118: 1325–1329. 10.1002/ijc.21486PubMedCrossRef
3.
go back to reference Smith T, Stein KD, Mehta CC, Kaw C, Kepner JL, Buskirk T, Stafford J, Baker F: The rationale, design, and implementation of the American Cancer Society's studies of cancer survivors. Cancer 2007, 109: 1–12. 10.1002/cncr.22387PubMedCrossRef Smith T, Stein KD, Mehta CC, Kaw C, Kepner JL, Buskirk T, Stafford J, Baker F: The rationale, design, and implementation of the American Cancer Society's studies of cancer survivors. Cancer 2007, 109: 1–12. 10.1002/cncr.22387PubMedCrossRef
4.
go back to reference Wu F, Safe S: Differential activation of wild-type estrogen receptor alpha and C-terminal deletion mutants by estrogens, antiestrogens and xenoestrogens in breast cancer cells. J Steroid Biochem Mol Biol 2007, 103: 1–9. 10.1016/j.jsbmb.2006.07.007PubMedCrossRef Wu F, Safe S: Differential activation of wild-type estrogen receptor alpha and C-terminal deletion mutants by estrogens, antiestrogens and xenoestrogens in breast cancer cells. J Steroid Biochem Mol Biol 2007, 103: 1–9. 10.1016/j.jsbmb.2006.07.007PubMedCrossRef
5.
go back to reference Liu L, Yu XZ, Li TS, Song LX, Chen PL, Suo TL, Li YH, Wang SD, Chen Y, Ren YM, et al.: A novel protein tyrosine kinase NOK that shares homology with platelet- derived growth factor/fibroblast growth factor receptors induces tumorigenesis and metastasis in nude mice. Cancer Res 2004, 64: 3491–3499. 10.1158/0008-5472.CAN-03-2106PubMedCrossRef Liu L, Yu XZ, Li TS, Song LX, Chen PL, Suo TL, Li YH, Wang SD, Chen Y, Ren YM, et al.: A novel protein tyrosine kinase NOK that shares homology with platelet- derived growth factor/fibroblast growth factor receptors induces tumorigenesis and metastasis in nude mice. Cancer Res 2004, 64: 3491–3499. 10.1158/0008-5472.CAN-03-2106PubMedCrossRef
6.
go back to reference Li YH, Zhong S, Rong ZL, Ren YM, Li ZY, Zhang SP, Chang Z, Liu L: The carboxyl terminal tyrosine 417 residue of NOK has an autoinhibitory effect on NOK-mediated signaling transductions. Biochem Biophys Res Commun 2007, 356: 444–449. 10.1016/j.bbrc.2007.02.154PubMedCrossRef Li YH, Zhong S, Rong ZL, Ren YM, Li ZY, Zhang SP, Chang Z, Liu L: The carboxyl terminal tyrosine 417 residue of NOK has an autoinhibitory effect on NOK-mediated signaling transductions. Biochem Biophys Res Commun 2007, 356: 444–449. 10.1016/j.bbrc.2007.02.154PubMedCrossRef
8.
go back to reference Syed V, Ulinski G, Mok SC, Ho SM: Reproductive hormone-induced, STAT3-mediated interleukin 6 action in normal and malignant human ovarian surface epithelial cells. J Natl Cancer Inst 2002, 94: 617–629.PubMedCrossRef Syed V, Ulinski G, Mok SC, Ho SM: Reproductive hormone-induced, STAT3-mediated interleukin 6 action in normal and malignant human ovarian surface epithelial cells. J Natl Cancer Inst 2002, 94: 617–629.PubMedCrossRef
9.
go back to reference Chen Y, Li YH, Chen XP, Gong LM, Zhang SP, Chang ZJ, Zhang XF, Fu XY, Liu L: Point mutation at single tyrosine residue of novel oncogene NOK abrogates tumorigenesis in nude mice. Cancer Res 2005, 65: 10838–10846. 10.1158/0008-5472.CAN-05-1091PubMedCrossRef Chen Y, Li YH, Chen XP, Gong LM, Zhang SP, Chang ZJ, Zhang XF, Fu XY, Liu L: Point mutation at single tyrosine residue of novel oncogene NOK abrogates tumorigenesis in nude mice. Cancer Res 2005, 65: 10838–10846. 10.1158/0008-5472.CAN-05-1091PubMedCrossRef
10.
go back to reference Kimbro KS, Duschene K, Willard M, Moore JA, Freeman S: A novel gene STYK1/NOK is upregulated in estrogen receptor-alpha negative estrogen receptor-beta positive breast cancer cells following estrogen treatment. Mol Biol Rep 2008, 35: 23–27. 10.1007/s11033-006-9047-1PubMedCrossRef Kimbro KS, Duschene K, Willard M, Moore JA, Freeman S: A novel gene STYK1/NOK is upregulated in estrogen receptor-alpha negative estrogen receptor-beta positive breast cancer cells following estrogen treatment. Mol Biol Rep 2008, 35: 23–27. 10.1007/s11033-006-9047-1PubMedCrossRef
11.
go back to reference Cunat S, Hoffmann P, Pujol P: Estrogens and epithelial ovarian cancer. Gynecol Oncol 2004, 94: 25–32. 10.1016/j.ygyno.2004.03.026PubMedCrossRef Cunat S, Hoffmann P, Pujol P: Estrogens and epithelial ovarian cancer. Gynecol Oncol 2004, 94: 25–32. 10.1016/j.ygyno.2004.03.026PubMedCrossRef
12.
go back to reference Roa BR, Slotman BJ: Action and counter-action of hormones in human ovarian cancer. Anticancer Res 1989, 9: 1005–1007.PubMed Roa BR, Slotman BJ: Action and counter-action of hormones in human ovarian cancer. Anticancer Res 1989, 9: 1005–1007.PubMed
13.
go back to reference Backstrom T, Sanders D, Leask R, Davidson D, Warner P, Bancroft J: Mood, sexuality, hormones, and the menstrual cycle. II. Hormone levels and their relationship to the premenstrual syndrome. Psychosom Med 1983, 45: 503–507.PubMedCrossRef Backstrom T, Sanders D, Leask R, Davidson D, Warner P, Bancroft J: Mood, sexuality, hormones, and the menstrual cycle. II. Hormone levels and their relationship to the premenstrual syndrome. Psychosom Med 1983, 45: 503–507.PubMedCrossRef
14.
go back to reference Mahlck CG, Backstrom T, Kjellgren O: Androstenedione production by malignant epithelial ovarian tumors. Gynecol Oncol 1986, 25: 217–222. 10.1016/0090-8258(86)90102-2PubMedCrossRef Mahlck CG, Backstrom T, Kjellgren O: Androstenedione production by malignant epithelial ovarian tumors. Gynecol Oncol 1986, 25: 217–222. 10.1016/0090-8258(86)90102-2PubMedCrossRef
15.
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 17beta-estradiol and selective GPR30 ligand G-1 in ovarian cancer cells. Cancer Res 2007, 67: 1859–1866. 10.1158/0008-5472.CAN-06-2909PubMedCrossRef 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 17beta-estradiol and selective GPR30 ligand G-1 in ovarian cancer cells. Cancer Res 2007, 67: 1859–1866. 10.1158/0008-5472.CAN-06-2909PubMedCrossRef
16.
go back to reference Yalcin A: Quantification of thioredoxin mRNA expression in the rat hippocampus by real-time PCR following oxidative stress. Acta Biochim Pol 2004, 51: 1059–1065.PubMed Yalcin A: Quantification of thioredoxin mRNA expression in the rat hippocampus by real-time PCR following oxidative stress. Acta Biochim Pol 2004, 51: 1059–1065.PubMed
17.
go back to reference Moriai R, Kobayashi D, Amachika T, Tsuji N, Watanabe N: Diagnostic relevance of overexpressed NOK mRNA in breast cancer. Anticancer Res 2006, 26: 4969–4973.PubMed Moriai R, Kobayashi D, Amachika T, Tsuji N, Watanabe N: Diagnostic relevance of overexpressed NOK mRNA in breast cancer. Anticancer Res 2006, 26: 4969–4973.PubMed
18.
go back to reference Amachika T, Kobayashi D, Moriai R, Tsuji N, Watanabe N: Diagnostic relevance of overexpressed mRNA of novel oncogene with kinase-domain (NOK) in lung cancers. Lung Cancer 2007, 56: 337–340. 10.1016/j.lungcan.2007.01.002PubMedCrossRef Amachika T, Kobayashi D, Moriai R, Tsuji N, Watanabe N: Diagnostic relevance of overexpressed mRNA of novel oncogene with kinase-domain (NOK) in lung cancers. Lung Cancer 2007, 56: 337–340. 10.1016/j.lungcan.2007.01.002PubMedCrossRef
19.
go back to reference Kondoh T, Kobayashi D, Tsuji N, Kuribayashi K, Watanabe N: Overexpression of serine threonine tyrosine kinase 1/novel oncogene with kinase domain mRNA in patients with acute leukemia. Exp Hematol 2009, 37: 824–830. 10.1016/j.exphem.2009.04.010PubMedCrossRef Kondoh T, Kobayashi D, Tsuji N, Kuribayashi K, Watanabe N: Overexpression of serine threonine tyrosine kinase 1/novel oncogene with kinase domain mRNA in patients with acute leukemia. Exp Hematol 2009, 37: 824–830. 10.1016/j.exphem.2009.04.010PubMedCrossRef
20.
go back to reference O'Donnell AJ, Macleod KG, Burns DJ, Smyth JF, Langdon SP: Estrogen receptor-alpha mediates gene expression changes and growth response in ovarian cancer cells exposed to estrogen. Endocr Relat Cancer 2005, 12: 851–866. 10.1677/erc.1.01039PubMedCrossRef O'Donnell AJ, Macleod KG, Burns DJ, Smyth JF, Langdon SP: Estrogen receptor-alpha mediates gene expression changes and growth response in ovarian cancer cells exposed to estrogen. Endocr Relat Cancer 2005, 12: 851–866. 10.1677/erc.1.01039PubMedCrossRef
21.
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. 10.1095/biolreprod.108.071175PubMedCrossRef 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. 10.1095/biolreprod.108.071175PubMedCrossRef
22.
go back to reference Funakoshi T, Yanai A, Shinoda K, Kawano MM, Mizukami Y: G protein-coupled receptor 30 is an estrogen receptor in the plasma membrane. Biochem Biophys Res Commun 2006, 346: 904–910. 10.1016/j.bbrc.2006.05.191PubMedCrossRef Funakoshi T, Yanai A, Shinoda K, Kawano MM, Mizukami Y: G protein-coupled receptor 30 is an estrogen receptor in the plasma membrane. Biochem Biophys Res Commun 2006, 346: 904–910. 10.1016/j.bbrc.2006.05.191PubMedCrossRef
Metadata
Title
Aberrant STYK1 expression in ovarian cancer tissues and cell lines
Authors
Kesmic A Jackson
Gabriela Oprea
Jeffrey Handy
K Sean Kimbro
Publication date
01-12-2009
Publisher
BioMed Central
Published in
Journal of Ovarian Research / Issue 1/2009
Electronic ISSN: 1757-2215
DOI
https://doi.org/10.1186/1757-2215-2-15

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