Control of Differentiation, Transformation, and Apoptosis in Granulosa Cells by Oncogenes, Oncoviruses, and Tumor Suppressor Genes1
Abraham Amsterdam and
Natarajagounder Selvaraj2
Department of Molecular Cell Biology, The Weizmann Institute of
Science, Rehovot 76100, Israel
I. Introduction
II. Protooncogene Expression and FollicularCell Development
A. Expression of myc, jun, and
fos in granulosacells
B. Expression of c-kit protooncogene and its ligand
steel/kitin the ovary
III. Tumor Suppressor Genes, Death Genes, andSurvival Genesin Granulosa
Cells
A. Expression of Fas antigenand its ligand in the ovary
B. Modulation of gene expression
IV. Immortalization of Primary Granulosa Cells by Oncogenesand Oncoviruses
A. Establishment of immortalized granulosacells expressing
gonadotropinreceptors
V. Mechanism of Inductionof Differentiation in Oncogene-Transformed
Cells
A. Expressionof adrenal 4-binding protein/steroidogenic factor-1
B. Expressionof steroidogenic acute regulatory protein
C. Expression ofsterol carrier protein 2 and the peripheral
benzodiazepinereceptor
D. Induction of steroidogenesis in immortalized granulosacells
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 ovariangranulosa cells
C. The role of protooncogenes and tumor suppressorgenes inovarian cancer
VII. Conclusions
VIII. Future Directions
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