HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (23) Citing Articles via Google Scholar Google Scholar Articles by Choi, J.-H. Articles by Leung, P. C K Search for Related Content PubMed PubMed Citation Articles by Choi, J.-H. Articles by Leung, P. C K

Department of Obstetrics and Gynecology, British Columbia Children’s and Women’s Hospital, British Columbia Research Institute for Children’s and Women’s Health, University of British Columbia, Vancouver, British Columbia, Canada V6H 3V5

(Requests for offprints should be addressed to P C K Leung; Email: peleung{at}interchange.ubc.ca)

Gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) have been implicated as probable risk factors in epithelial ovarian carcinomas, most of which are derived from ovarian surface epithelium (OSE). Since epidermal growth factor (EGF) increases the growth of ovarian surface epithelial cells, we determined the effect of gonadotropins on the expression of epidermal growth factor receptor (EGFR). We investigated the basal levels of EGFR mRNA and protein, and the mechanisms involved in the regulation of EGFR at the transcriptional and translational levels by FSH and LH. The immortalized OSE cell lines (IOSE) derived from normal OSE cells by transfecting SV40 T-antigen (IOSE-80 and IOSE-80PC, a post-crisis line) and ovarian cancer cell lines were employed. A significantly lower level of EGFR was observed in both IOSE-80 and IOSE-80PC cells when compared with the ovarian cancer cell lines, OVCAR-3 and SKOV-3. Treatment of IOSE-80PC cells with FSH and LH (10^–7 and 10^–6 g/ml) resulted in a significant increase in EGFR mRNA at 24 h and EGFR protein at 48 h, whereas the treatment with gonadotropins for 24–48 h induced a mild increase in EGFR in OVCAR-3, but not in SKOV-3 cells. In addition, IOSE-80PC cells treated with gonadotropins and EGF (10 nM) exhibited an additive stimulation of mitogenesis. Further, FSH and LH significantly increased activities of various kinases at 5–10 min, and pre-treatments with LY294002 (an inhibitor of PI3K) or PD98059 (an inhibitor of ERK1/2) partially blocked the gonadotropin-induced up-regulation of EGFR in IOSE-80PC cells. We investigated whether the effect of gonadotropins on EGFR mRNA levels is induced by increased transcription and/or by altered mRNA stability. Treatment of IOSE-80PC cells with FSH (10^–7 and 10^–6 g/ml) significantly enhanced the activity of the EGFR promoter (120 and 140% increase, respectively) at 24 h, and treatment with LH (10^–7 g/ml) for 24 h induced an increase in the activity of EGFR promoter (30%) in these cells. On the other hand, LH resulted in a significant increase in EGFR mRNA stability in the decay curves. Taken together, these results suggest that the effect of gonadotropins on the expression of EGFR may affect cell growth via ERK-1/-2 and PI3K pathways in pre-neoplastic ovarian surface epithelial cells, and that FSH and LH increase EGFR mRNA by different mechanisms. The former increased EGFR gene transcription essentially, whereas the latter mainly enhanced EGFR mRNA stability.

This article has been cited by other articles:

				J.-H. Choi, C.-L. Chen, S. L. Poon, H.-S. Wang, and P. C K Leung Gonadotropin-stimulated epidermal growth factor receptor expression in human ovarian surface epithelial cells: involvement of cyclic AMP-dependent exchange protein activated by cAMP pathway Endocr. Relat. Cancer, March 1, 2009; 16(1): 179 - 188. [Abstract] [Full Text] [PDF]

				S. W. Warrenfeltz, S. A. Lott, T. M. Palmer, J. C. Gray, and D. Puett Luteinizing Hormone-Induced Up-Regulation of ErbB-2 Is Insufficient Stimulant of Growth and Invasion in Ovarian Cancer Cells Mol. Cancer Res., November 1, 2008; 6(11): 1775 - 1785. [Abstract] [Full Text] [PDF]

				M. Assidi, I. Dufort, A. Ali, M. Hamel, O. Algriany, S. Dielemann, and M.-A. Sirard Identification of Potential Markers of Oocyte Competence Expressed in Bovine Cumulus Cells Matured with Follicle-Stimulating Hormone and/or Phorbol Myristate Acetate In Vitro Biol Reprod, August 1, 2008; 79(2): 209 - 222. [Abstract] [Full Text] [PDF]

				J.-H. Choi, A. S. T. Wong, H.-F. Huang, and P. C. K. Leung Gonadotropins and Ovarian Cancer Endocr. Rev., June 1, 2007; 28(4): 440 - 461. [Abstract] [Full Text] [PDF]

				D. L. Russell and R. L. Robker Molecular mechanisms of ovulation: co-ordination through the cumulus complex Hum. Reprod. Update, May 1, 2007; 13(3): 289 - 312. [Abstract] [Full Text] [PDF]

				J. J. Schumacher, R. P.M. Dings, J. Cosin, I. V. Subramanian, N. Auersperg, and S. Ramakrishnan Modulation of Angiogenic Phenotype Alters Tumorigenicity in Rat Ovarian Epithelial Cells Cancer Res., April 15, 2007; 67(8): 3683 - 3690. [Abstract] [Full Text] [PDF]

				P. C.K. Leung and J.-H. Choi Endocrine signaling in ovarian surface epithelium and cancer Hum. Reprod. Update, March 1, 2007; 13(2): 143 - 162. [Abstract] [Full Text] [PDF]

				Y. L. Pon and A. S. T. Wong Gonadotropin-Induced Apoptosis in Human Ovarian Surface Epithelial Cells Is Associated with Cyclooxygenase-2 Up-Regulation via the {beta}-Catenin/T-Cell Factor Signaling Pathway Mol. Endocrinol., December 1, 2006; 20(12): 3336 - 3350. [Abstract] [Full Text] [PDF]

				O Gubbay, M T Rae, A S McNeilly, F X Donadeu, A J Zeleznik, and S G Hillier cAMP response element-binding (CREB) signalling and ovarian surface epithelial cell survival. J. Endocrinol., October 1, 2006; 191(1): 275 - 285. [Abstract] [Full Text] [PDF]

				J.-H. Choi, K.-C. Choi, N. Auersperg, and P. C K Leung Differential regulation of two forms of gonadotropin-releasing hormone messenger ribonucleic acid by gonadotropins in human immortalized ovarian surface epithelium and ovarian cancer cells. Endocr. Relat. Cancer, June 1, 2006; 13(2): 641 - 651. [Abstract] [Full Text] [PDF]

				J.-H. Choi, K.-C. Choi, N. Auersperg, and P. C.K. Leung Gonadotropins Activate Proteolysis and Increase Invasion through Protein Kinase A and Phosphatidylinositol 3-Kinase Pathways in Human Epithelial Ovarian Cancer Cells. Cancer Res., April 1, 2006; 66(7): 3912 - 3920. [Abstract] [Full Text] [PDF]