This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints, Permissions and Rights Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Amsterdam, A. Articles by Selvaraj, N. Search for Related Content PubMed PubMed Citation Articles by Amsterdam, A. Articles by Selvaraj, N.

Control of Differentiation, Transformation, and Apoptosis in Granulosa Cells by Oncogenes, Oncoviruses, and Tumor Suppressor Genes¹

Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel

I. Introduction

II. Protooncogene Expression and Follicular Cell Development

A. Expression of myc, jun, and fos in granulosa cells

B. Expression of c-kit protooncogene and its ligand steel/kit in the ovary

III. Tumor Suppressor Genes, Death Genes, and Survival Genes in Granulosa Cells

A. Expression of Fas antigen and its ligand in the ovary

B. Modulation of gene expression

IV. Immortalization of Primary Granulosa Cells by Oncogenes and Oncoviruses

A. Establishment of immortalized granulosa cells expressing gonadotropin receptors

V. Mechanism of Induction of Differentiation in Oncogene-Transformed Cells

A. Expression of adrenal 4-binding protein/steroidogenic factor-1

B. Expression of steroidogenic acute regulatory protein

C. Expression of sterol carrier protein 2 and the peripheral benzodiazepine receptor

D. Induction of steroidogenesis in immortalized granulosa cells

E. Expression of inhibin, activin, and follistatin

F. Involvement of the cytoskeleton in granulosa cell differentiation, transformation, and programmed cell death

VI. Ovarian Cancer

A. Endocrine factors in ovarian cancer

B. Tumors of ovarian granulosa cells

C. The role of protooncogenes and tumor suppressor genes in ovarian cancer

VII. Conclusions

VIII. Future Directions

This article has been cited by other articles:

				B. S. Middlebrook, K. Eldin, X. Li, S. Shivasankaran, and S. A. Pangas Smad1-Smad5 Ovarian Conditional Knockout Mice Develop a Disease Profile Similar to the Juvenile Form of Human Granulosa Cell Tumors Endocrinology, December 1, 2009; 150(12): 5208 - 5217. [Abstract] [Full Text] [PDF]

				M. Bilandzic, S. Chu, P. G. Farnworth, C. Harrison, P. Nicholls, Y. Wang, R. M. Escalona, P. J. Fuller, J. K. Findlay, and K. L. Stenvers Loss of Betaglycan Contributes to the Malignant Properties of Human Granulosa Tumor Cells Mol. Endocrinol., April 1, 2009; 23(4): 539 - 548. [Abstract] [Full Text] [PDF]

				J. J. Peluso, X. Liu, and J. Romak Progesterone Maintains Basal Intracellular Adenosine Triphosphate Levels and Viability of Spontaneously Immortalized Granulosa Cells by Promoting an Interaction between 14-3-3{sigma} and ATP Synthase{beta}/Precursor through a Protein Kinase G-Dependent Mechanism Endocrinology, May 1, 2007; 148(5): 2037 - 2044. [Abstract] [Full Text] [PDF]

				N. Kalfa, A. Ecochard, C. Patte, P. Duvillard, F. Audran, C. Pienkowski, E. Thibaud, R. Brauner, C. Lecointre, D. Plantaz, et al. Activating Mutations of the Stimulatory G Protein in Juvenile Ovarian Granulosa Cell Tumors: A New Prognostic Factor? J. Clin. Endocrinol. Metab., May 1, 2006; 91(5): 1842 - 1847. [Abstract] [Full Text] [PDF]

				S. B Rulli and I. Huhtaniemi What have gonadotrophin overexpressing transgenic mice taught us about gonadal function? Reproduction, September 1, 2005; 130(3): 283 - 291. [Abstract] [Full Text] [PDF]

				J.J. Peluso and A. Pappalardo Progesterone Regulates Granulosa Cell Viability Through a Protein Kinase G-Dependent Mechanism That May Involve 14-3-3{sigma} Biol Reprod, December 1, 2004; 71(6): 1870 - 1878. [Abstract] [Full Text] [PDF]

				C. K. Ong, C. Y. Ng, C. Leong, C. P. Ng, C. S. Ong, T. T. T. Nguyen, and H. Huynh Structural Characterization of Three Novel Rat OKL38 Transcripts, Their Tissue Distributions, and Their Regulation by Human Chorionic Gonadotropin Endocrinology, October 1, 2004; 145(10): 4763 - 4774. [Abstract] [Full Text] [PDF]

				W. E. Thompson, E. Asselin, A. Branch, J. K. Stiles, P. Sutovsky, L. Lai, G.-S. Im, R. S. Prather, S. C. Isom, E. Rucker III, et al. Regulation of Prohibitin Expression During Follicular Development and Atresia in the Mammalian Ovary Biol Reprod, July 1, 2004; 71(1): 282 - 290. [Abstract] [Full Text] [PDF]

				R. Sasson, E. Rimon, A. Dantes, T. Cohen, V. Shinder, A. Land-Bracha, and A. Amsterdam Gonadotrophin-induced gene regulation in human granulosa cells obtained from IVF patients. Modulation of steroidogenic genes, cytoskeletal genes and genes coding for apoptotic signalling and protein kinases Mol. Hum. Reprod., May 1, 2004; 10(5): 299 - 311. [Abstract] [Full Text] [PDF]

				R. SASSON, A. DANTES, K. TAJIMA, and A. AMSTERDAM Novel genes modulated by FSH in normal and immortalized FSH-responsive cells: new insights into the mechanism of FSH action FASEB J, July 1, 2003; 17(10): 1256 - 1266. [Abstract] [Full Text] [PDF]

				I. Rothchild The Yolkless Egg and the Evolution of Eutherian Viviparity Biol Reprod, February 1, 2003; 68(2): 337 - 357. [Abstract] [Full Text] [PDF]

				R. J. Mann, R. A. Keri, and J. H. Nilson Consequences of Elevated Luteinizing Hormone on Diverse Physiological Systems: Use of the LH{beta}CTP Transgenic Mouse as a Model of Ovarian Hyperstimulation-induced Pathophysiology Recent Prog. Horm. Res., January 1, 2003; 58(1): 343 - 375. [Abstract] [Full Text] [PDF]

				G. E. Owens, R. A. Keri, and J. H. Nilson Ovulatory Surges of Human CG Prevent Hormone-Induced Granulosa Cell Tumor Formation Leading to the Identification of Tumor-Associated Changes in the Transcriptome Mol. Endocrinol., June 1, 2002; 16(6): 1230 - 1242. [Abstract] [Full Text] [PDF]

				K. Tajima, M. Orisaka, K. Hosokawa, A. Amsterdam, and F. Kotsuji Effects of Ovarian Theca Cells on Apoptosis and Proliferation of Granulosa Cells: Changes During Bovine Follicular Maturation Biol Reprod, June 1, 2002; 66(6): 1635 - 1639. [Abstract] [Full Text] [PDF]

				S. Fritz, L. Kunz, N. Dimitrijevic, R. Grunert, C. Heiss, and A. Mayerhofer Muscarinic Receptors in Human Luteinized Granulosa Cells: Activation Blocks Gap Junctions and Induces the Transcription Factor Early Growth Response Factor-1 J. Clin. Endocrinol. Metab., March 1, 2002; 87(3): 1362 - 1367. [Abstract] [Full Text] [PDF]

				K. Tajima, K. Hosokawa, Y. Yoshida, A. Dantes, R. Sasson, F. Kotsuji, and A. Amsterdam Establishment of FSH-responsive cell lines by transfection of pre-ovulatory human granulosa cells with mutated p53 (p53val135) and Ha-ras genes Mol. Hum. Reprod., January 1, 2002; 8(1): 48 - 57. [Abstract] [Full Text] [PDF]

				A. Amsterdam, K. Kannan, D. Givol, Y. Yoshida, K. Tajima, and A. Dantes Apoptosis of Granulosa Cells and Female Infertility in Achondroplastic Mice Expressing Mutant Fibroblast Growth Factor Receptor 3G374R Mol. Endocrinol., September 1, 2001; 15(9): 1610 - 1623. [Abstract] [Full Text] [PDF]

				R. Sasson, K. Tajima, and A. Amsterdam Glucocorticoids Protect against Apoptosis Induced by Serum Deprivation, Cyclic Adenosine 3',5'-Monophosphate and p53 Activation in Immortalized Human Granulosa Cells: Involvement of Bcl-2 Endocrinology, February 1, 2001; 142(2): 802 - 811. [Abstract] [Full Text] [PDF]

				Y. Nishi, T. Yanase, Y.-M. Mu, K. Oba, I. Ichino, M. Saito, M. Nomura, C. Mukasa, T. Okabe, K. Goto, et al. Establishment and Characterization of a Steroidogenic Human Granulosa-Like Tumor Cell Line, KGN, That Expresses Functional Follicle-Stimulating Hormone Receptor Endocrinology, January 1, 2001; 142(1): 437 - 445. [Abstract] [Full Text] [PDF]

				B. Sommersberg, A. Bulling, U. Salzer, U. Fröhlich, R. E. Garfield, A. Amsterdam, and A. Mayerhofer Gap Junction Communication and Connexin 43 Gene Expression in a Rat Granulosa Cell Line: Regulation by Follicle-Stimulating Hormone Biol Reprod, December 1, 2000; 63(6): 1661 - 1668. [Abstract] [Full Text]

				A. Schultze-Mosgau, A. C. Katzur, K. K. Arora, S. S. Stojilkovic, K. Diedrich, and O. Ortmann Characterization of calcium-mobilizing, purinergic P2Y2 receptors in human ovarian cancer cells Mol. Hum. Reprod., May 1, 2000; 6(5): 435 - 442. [Abstract] [Full Text] [PDF]

				J. A. McCracken, E. E. Custer, and J. C. Lamsa Luteolysis: A Neuroendocrine-Mediated Event Physiol Rev, April 1, 1999; 79(2): 263 - 323. [Abstract] [Full Text] [PDF]

				K. Hosokawa, A. Dantes, C. Schere-Levy, A. Barash, Y. Yoshida, F. Kotsuji, I. Vlodavsky, and A. Amsterdam Induction of Ad4BP/SF-1, Steroidogenic Acute Regulatory Protein, and Cytochrome P450scc Enzyme System Expression in Newly Established Human Granulosa Cell Lines Endocrinology, November 1, 1998; 139(11): 4679 - 4687. [Abstract] [Full Text] [PDF]

				K. Hosokawa, D. Aharoni, A. Dantes, E. Shaulian, C. Schere-Levy, R. Atzmon, F. Kotsuji, M. Oren, I. Vlodavsky, and A. Amsterdam Modulation of Mdm2 Expression and p53-Induced Apoptosis in Immortalized Human Ovarian Granulosa Cells Endocrinology, November 1, 1998; 139(11): 4688 - 4700. [Abstract] [Full Text] [PDF]

				R. Seger, T. Hanoch, R. Rosenberg, A. Dantes, W. E. Merz, J. F. Strauss III, and A. Amsterdam The ERK Signaling Cascade Inhibits Gonadotropin-stimulated Steroidogenesis J. Biol. Chem., April 20, 2001; 276(17): 13957 - 13964. [Abstract] [Full Text] [PDF]