Role of Mammalian Homologs of the Drosophila Discs Large 1 (dlg 1) Gene in the Genesis of Epithelial Ovarian Cancer.

摘要

We implemented an approach toward investigating the development and progression of ovarian cancer that involved 'species hopping'. This approach made use of strong genotype-phenotype correlations in Drosophila melanogaster to identify a fly tumor suppressor gene, discs large 1 (digi), whose mouse homologs could serve as candidates for study into the etiology of mammalian ovarian cancer. The proposed study was designed (1) to identify digi homologs whose gene products were localized to the cells of the ovarian surface epithelium (0 SE), (2) to generate mice bearing a systemic deletion of a digi homolog normally expressed in the OSE, and (3) to characterize the ovarian phenotype resulting from such systemic deletion of the selected homolog. As a result of effort toward accomplishing the first goal, protein products of the mouse genes SAP 102 and ZO-l were identified by immunodetection in granulosa cells, but not in OSE. ZO-3 protein was identified by immunodetection in oviduct lumen epithelium, but not in OSE. Both ZO-2 and CASK proteins were immunodetected in OSE, but were also present in other ovarian cell types. Efforts at localizing the Dlghi, Dlgh2, Dlgh3, pS5 and PSD95 proteins are ongoing and may yet provide a candidate for further study by systemic deletion.