Etiology of ovarian cancer: a proposed mechanism.

The majority of ovarian cancers are derived from ovarian surface epithelial cells that are sequestered in inclusion cysts within the ovarian stroma. We propose that the Fas/Fas ligand system is responsible for the normal elimination of these inclusion cysts through apoptosis, thereby removing potential sites of ovarian tumors. Furthermore, we hypothesize that the failure of the Fas/Fas ligand's apoptotic signaling mechanism leads to the persistence of these inclusion cysts in the stroma, and the onset of ovarian tumorigenesis.

Activation of Fas ligand/receptor system kills ovarian cancer cell lines by an apoptotic mechanism.

The majority of ovarian cancers originate from the surface epithelium of the ovary and from inclusion cysts derived from the epithelium that becomes sequestered in the stroma. To identify naturally occurring ligands that could activate mechanisms by which these ovarian neoplasms could be eliminated, we have examined the ability of anti-Fas mAb to induce apoptosis in two cell lines, HEY and Caov-3, derived from ovarian carcinomas of surface epithelial origin. Treatment of each cell line with anti-Fas mAb caused chromatin condensation, nuclear segmentation, and apoptotic body formation, indicative of apoptosis.

Induction of apoptosis in thecal/interstitial cells: action of transforming growth factor (TGF) alpha plus TGF beta on bcl-2 and interleukin-1 beta-converting enzyme.

Follicular atresia is characterized by the initial rapid loss of granulosa cells by apoptosis, followed by the loss of thecal cells at a slower rate. We have previously shown that treatment of subconfluent cultures of thecal/interstitial cells (T/I) with transforming growth factor (TGF) alpha plus TGF beta caused chromatin condensation and internucleosomal fragmentation characteristic of apoptosis, whereas in the presence of either TGF alpha or TGF beta alone the cells remained healthy. In this study we have examined the effect of TGF alpha and TGF beta alone and in combination on the levels of mRNA encoding bcl-2 and interleukin-1 beta-converting enzyme (ICE) in T/I cells using a semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) assay.

Fas-induced apoptosis in rat thecal/interstitial cells signals through sphingomyelin-ceramide pathway.

Of the ovarian follicles that develop during reproductive life, more than 99% do not ovulate and are eliminated from the ovary by follicular atresia. Atresia is achieved by the self destruction of thecal and granulosa cells that comprise the follicle, by the process of apoptosis. The objective of this study was to determine if activation of the Fas receptor could enact apoptosis of thecal cells, and to explore the signal transduction pathway involved.

Induction of apoptosis in rat thecal/interstitial cells by transforming growth factor alpha plus transforming growth factor beta in vitro.

In each estrous cycle dominant follicles are selected from a growing pool to develop to the preovulatory stage and to ovulate. Those follicles that do not ovulate must be eliminated in order to maintain the constant mass and homeostasis of the ovary. Granulosa cells are lost by apoptosis at the onset of follicular atresia, whereas apoptotic thecal cells are identified at later stages of atresia.