Ovarian Cancer ranks 4th as the cause of cancer deaths in women in the US, accounting for more deaths than any other gynecologic cancer, having a 5 year survival rate of only 44%. It is imperative that improved approaches to diagnosing ovarian cancers are found, including the identification of applicable molecular markers. The paired-box (PAX) genes encode a family of transcription factors with critical roles in the formation of tissues and organs during embryogenesis. These transcription factors regulate expression of gene products that control cell proliferation and differentiation. Since these processes are also essential to the development of cancer, it follows that PAX genes may participate in the initiation and proliferation of cancer. PAX8, a transcription factor predominately responsible for regulation of gene expression in the thyroid and kidney, has been shown as a highly expressed gene in Wilms’ Tumors and thyroid follicular carcinomas. In recent studies, PAX8 has been linked to ovarian tumors as well. In our study we evaluated PAX8 expression in normal tissue, benign neoplasms, and malignant epithelial tumors of the ovary. Microarray analysis (MA) of mRNA from human ovarian tissues was performed on 65 ovarian samples and 2 cell lines. Gene expression was assessed using Affymetrix Human Genome Focus GeneChip microarrays to characterize differences in gene expression between the three tissue types. Real-Time RT-PCR (qRT-PCR) was used to verify the PAX8 expression patterns demonstrated by microarray data. Additionally, western blotting (WB) and Immunohistochemistry (IHC) were used to visualize the effect of increased transcription on the PAX8 protein complement within representative tissues. MA revealed a consistently higher level of PAX8 expression in the benign and malignant groups when compared to normal ovarian samples. Fold changes of +1.18 and + 3.32 were shown when comparing normal samples to benign and malignant samples respectively. Our validation strategies uphold this observation, with qRT-PCR demonstrating these same trends of expression across tissue types. WB and IHC suggest that the expression patterns of PAX8 in ovarian tissues is translated to the protein component of these tissues, with higher levels in malignant samples as compared to normal and benign ovary. Tumorigenesis is a complex process involving the abnormal expression of many regulatory genes. Our results indicate that the transcriptional regulator PAX8 is intimately involved in the progression of ovarian carcinomas, and is a candidate as a diagnostic biomarker.
[Proc Amer Assoc Cancer Res, Volume 47, 2006]