Compared to the normal OSE cells, the OvCa samples showed 2. 71 and 2. 22 fold reduced expression of TMEM97 when SNRP70 and GAPDH were used as control genes, respec tively. To test for somatic mutations in the TMEM97 gene, which is located on chromosome band 17q11. 2, we sequenced all of the coding nucleotides, that are dis tributed to three www.selleckchem.com/products/Bortezomib.html exons, in 39 ovarian cancer samples. We found an intronic single nucleotide polymorphism in a single sample but no coding sequence vari ations. Discussion To determine the intracellular gene targets of P4 in non neoplastic OSE cells, we analyzed changes in gene expres sion patterns in six independent short term cultures using genome wide transcript arrays. We found a highly statisti cally significant regulation of transcripts involved in cho lesterol metabolism.

For example, multiple transcripts representing cholesterol homeostasis genes including HMGCS1, HMGCR, IDI1, FDPS, FDFT1, NSDHL, EBP, DHCR7, INSIG1, FADS1 were upregulated by P4 exposure. Examination of each experimental pair revealed that the transcriptional activity induced by P4 exposure originated only Inhibitors,Modulators,Libraries from three of the six experi mental pairs. Re analysis of these three responder pairs uncovered a functionally uncharacterized gene TMEM97 as the most responsive transcript which showed a 1. 95 fold increase upon P4 exposure. Inhibitors,Modulators,Libraries Examination of genome scale, tissue specific gene expression levels in the GNF2 database uncovered a strong correlation between TMEM97 and cholesterol biosynthesis genes. This finding and our current microarray analyses suggest that TMEM97 plays a role in cholesterol metabolism.

We also found that the expression of TMEM97 was downregulated 2. 4 fold in OvCa samples. Collectively, these findings suggest that P4 is Inhibitors,Modulators,Libraries involved in cholesterol metabolism in OSE cells. To our knowledge, P4 regulation of cholesterol homeostasis genes in OSE cells has not been previously suggested. An earlier work has shown suppression of a subset of the Inhibitors,Modulators,Libraries cho lesterol biosynthesis pathway genes by PR receptor inhib itors in rat periovulatory granulose cells suggesting that P4 regulation of cholesterol homeostasis could be, at least in part, receptor mediated. The lack of significant gene expression changes in three of the six experimental pairs suggests that the transcriptional response to P4 may not be universal among OSE cells, at least under the experimental conditions described Inhibitors,Modulators,Libraries herein.

The reasons for this differential response are currently unclear. Analyses of two scientific assays genetic polymorphisms and the expression of PR gene did not reveal appreciable differ ences between the responder and non responder groups. Certain clinical characteristics such as history of oral con traceptive use, serum gonadotropin, estrogen or proges terone levels at the time of surgery might have influenced the responsiveness of the OSE cells to P4.