Differential BCCIP Gene Expression In Primary Human Ovarian Malignant Tumor, Renal Cell Carcinoma And Colorectal Cancer Tissues

Human BCCIP，a protein which interacts with BRCA2and CDKN1A (Cip1，p21)，has been implicated in many cellular processes including cell cycle regulation，DNArecombination and damage repair，telomere maintenance，embryonic development andgenomic stability. BCCIP gene expression，which is an important BRCA2cofactor intumor suppression，has been identified in some primary cancers. In this thesis，weinvestigated the role of BCCIP expression in a large sample of clinically diagnosedprimary ovarian cancer，renal cell carcinoma (RCC) and colorectal cancer (CRC) tissues.Using clinically diagnosed frozen primary cancer tissues，quantitative PCR (qPCR)，western blot analysis (WB) and immunohistochemical staining (IHC) approaches wereused to detect and measure gene expression.Conclusion:1. Reduction of BCCIP gene expression in ovarian cancer，RCC and CRC tissueswere occurred in74，89and75%，respectively.2. qPCR analysis of mRNA expression in the54ovarian cancer，50RCC and44CRC samples revealed significant (>2-fold decreased) BCCIP downregulation in56，70and46%of tissue samples，respectively.3. Although BCCIP expression in three different tumor tissues decreased，therelationship between BCCIP expression and clinicopathological features of each cancerwas distinct. Compared to normal tissues，BCCIP expression in ovarian cancers wassignificantly downregulated in serous， endometrioid and mucinous carcinomas.Downregulation of BCCIP expression was strongly associated with clear cell RCC(ccRCC) and Fuhrman tumor grading， but significant differences in BCCIP expression between CRC and matched normal tissues occurred only in male CRC tissues(p<0.05) and in tissue with a T4tumor stage (p<0.01). Thus，BCCIP protein was chieflyreduced in ovarian cancer and RCC tissue samples (p<0.05).4. BCCIP gene expression was downregulated in human ovarian cancer，RCC andCRC tissues，suggesting a role for the gene in the pathogenesis of these cancers.