Abstract

Studies in this grant period will focus on the hypothesis that chronic hypersecretion of LH, with a significant contribution from FSH, causes tumor formation by altering expression of a complex network of genes including a progressive down-regulation of the LH receptors and an increase in cyclin D2. The investigators will also map and clone the three non-allelic variants in the CF-1 genome necessary for GC tumorigenesis and contribute to its complete penetrance. In identifying gene expression profiles unique to the formation of granulosa cell tumors, these studies should contribute to a better understanding of permissive and causative events that underlie tumor formation.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA086387-06
Application #
6497462
Study Section
Biochemical Endocrinology Study Section (BCE)
Program Officer
Mietz, Judy
Project Start
2001-02-15
Project End
2006-01-31
Budget Start
2002-02-01
Budget End
2003-01-31
Support Year
6
Fiscal Year
2002
Total Cost
$309,825
Indirect Cost

  Institution

Name
Case Western Reserve University
Department
Pharmacology
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106

  Publications

Parakh, Tehnaz N; Hernandez, Jennifer A; Grammer, Jean C et al. (2006) Follicle-stimulating hormone/cAMP regulation of aromatase gene expression requires beta-catenin. Proc Natl Acad Sci U S A 103:12435-40
Mohammad, Helai P; Seachrist, Darcie D; Quirk, Christine C et al. (2004) Reexpression of p8 contributes to tumorigenic properties of pituitary cells and appears in a subset of prolactinomas in transgenic mice that hypersecrete luteinizing hormone. Mol Endocrinol 18:2583-93
Mann, Rachel J; Keri, Ruth A; Nilson, John H (2003) Consequences of elevated luteinizing hormone on diverse physiological systems: use of the LHbetaCTP transgenic mouse as a model of ovarian hyperstimulation-induced pathophysiology. Recent Prog Horm Res 58:343-75
Burns, Kathleen H; Owens, Gabe E; Ogbonna, Samuel C et al. (2003) Expression profiling analyses of gonadotropin responses and tumor development in the absence of inhibins. Endocrinology 144:4492-507
Mohammad, Helai P; Abbud, Rula A; Parlow, Al F et al. (2003) Targeted overexpression of luteinizing hormone causes ovary-dependent functional adenomas restricted to cells of the Pit-1 lineage. Endocrinology 144:4626-36
Owens, Gabe E; Keri, Ruth A; Nilson, John H (2002) 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 16:1230-42
Burns, Kathleen H; Owens, Gabe E; Fernandez, Julianna M et al. (2002) Characterization of integrin expression in the mouse ovary. Biol Reprod 67:743-51