OHSU

Jay W. Wright

The ovarian surface epithelium (OSE) is a small population of cells surrounding the ovary. This cellular monolayer comprises less than 1/1,000thof the entire ovary, yet gives rise to the majority of ovarian cancers in women. Among mammals, epithelial ovarian cancer has been reported only in primates, and as a consequence no animal models have been developed to date that adequately advance our understanding of ovarian cancer etiology.


It is our perspective that a more detailed investigation of the primate OSE will provide clues as to the mechanisms driving OSE transformation. Little is known about the primate OSE, and no role has been clearly established for these cells. Our current goals to study the OSE in vivoinclude (a) characterizing changes in the normal OSE in relation to the phase of the menstrual cycle and proximity to the site of ovulation, (b) to identify ovarian-derived cues that mediate OSE cellular processes (survival, proliferation, and death), and (c) to determine whether the OSE participates in ovarian processes (ovulation and tissue repair). Our long-term goals are focused on ovarian cancer prevention and early detection, in collaboration more clinically-oriented investigators.

Our current studies in vitroutilize cultured human and nonhuman primate OSE cells, and ovarian and breast cancer cell lines to investigate the effect of estrogen- and progesterone receptor ligands on novel activities of these receptors: in the local environment of the ovary, concentrations of estrogen and progesterone reach concentrations several orders of magnitude higher than are seen anywhere else in the body. These micromolar concentrations induce reversible cell cycle arrest and initiate apoptotic pathways (without inducing cell death). This natural response may be essential for protecting genetic integrity of the OSE in the genotoxic ovulatory environment and for preventing unregulated cell proliferation at the site of ovulation, both of which may be central to ovarian cancer etiology.

Research in our laboratory includes microarray analysis of human and nonhuman primate cells, inmmunohistochemistry and molecular approaches to study the effects of gene transfection on steroid hormone-mediated signal transduction, and whole animal studies to study the effects of the ovary and ovarian factors on the OSE, and the effects of the OSE on the ovary itself.

Translational efforts are currently evaluating the expression of genes that may be associated with hereditary risks of ovarian cancer (BRCA1/2 and FANCD2), with the objective of developing the nonhuman primate as a surrogate model to provide clinical options for ovarian cancer prevention and detection.

Key Publications

Wright, JW, T Pejovic, J Fanton and RL Stouffer. 2008. Induction of Proliferation in the Primate Ovarian Surface Epithelium in Vivo. Hum Reprod23:129-138.

Molskness, TA, DL Hess, GM Maginnis, JW Wright, JW Fanton and RL Stouffer. 2007. Characteristics and Regulation of the Ovarian Cycle in Vervet Monkeys (Chlorocebus Aethiops). Am J Primatol69:890-900.ADDIN BB

Wright, J. W., R. L. Stouffer and K. D. Rodland. 2005. High-Dose Estrogen and Clinical Selective Estrogen Receptor Modulators Induce Growth Arrest, P21, and P53 in Primate Ovarian Surface Epithelial Cells. J Clin Endocrinol Metab90:3688-3695.

Wright, J. W., R. L. Stouffer and K. D. Rodland. 2003. Estrogen Inhibits Cell Cycle Progression and Retinoblastoma Phosphorylation in Rhesus Ovarian Surface Epithelial Cell Culture. Mol Cell Endocrinol208:1-10.

Wright, J. W., S. Toth-Fejel, R. L. Stouffer and K. D. Rodland. 2002. Proliferation of Rhesus Ovarian Surface Epithelial Cells in Culture: Lack of Mitogenic Response to Steroid Or Gonadotropic Hormones. Endocrinology143:2198-2207.

 

See a full listing of Dr. Wright's publications