Ovarian cancer is the deadliest of the gynecologic cancers striking more than 25,000 American women and causing ∼16,000 deaths annually. However, the causes and mechanisms that lead to this fatal disease remain largely unknown. Previously, we reported that two splicing factors, polypyrimidine tract-binding protein (PTB) and SRp20, were overexpressed in ovarian tumor tissues compared to their matched normal tissues in ten pairs of matched specimens. Here we have examined the expression of these two splicing factors in another 19 pairs of matched ovarian tumor and normal tissues by western blot and confirmed our previous observation. In order to examine the expression of PTB and SRp20 at the cellular level, we performed immunohistochemistry staining for these two splicing factors on ovarian tumor tissue microarray, obtained from the Gynecologic Oncology Group (GOG) and with UIC IRB approval, on which there are 150 tumor tissue sections and 15 normal ovarian tissue sections. The 150 tumor sections came from 50 cases of late stage (stage III and IV) epithelial ovarian cancer with 3 spots for each case and distributed in the array randomly. The results show that most ovarian tumors are stained strongly for both PTB and SRp20 while normal ovarian tissues including surface epithelia are stained weakly or negatively. The detailed analysis of staining data is underway. Furthermore, we found that the expression of PTB and SRp20 were up-regulated in SV40 T antigen transduced ovarian surface epithelial cells (OSE), SV40 T antigen and human telomerase catalytic subunit (hTERT) sequentially transduced OSE and several ovarian cancer cell lines compared to normal human OSE. This observation suggests that the expression of PTB and SRp20 could be controlled by p53 and/or Rb, because SV40 T antigen inactivates these tumor suppressor genes. To further investigate the roles of splicing factors in ovarian tumorigenesis, we are now examining the effects of suppression of PTB and/or SRp20 by RNAi. (Supported in part by a subcontract from the GOG, and in part by CA30103 and CA40570 from NCI (to WTB)).

[Proc Amer Assoc Cancer Res, Volume 46, 2005]