Our research analyses the role of the EGF/erbB, and most recently the VEGF/KDR, gene family of receptors and ligands in the growth of ovarian carcinoma. The mRNA and protein expression of the EGF/erbB gene family was compared in five ovarian lines with three breat carcinoma cell lines leading to publication in June, 1999: Pegues, J.C., Kannan, B., and Stromberg, K.: erbB Receptor Expression and Growth Response to Heregulin in Five Ovarian Carcinoma Lines. Int. J. Oncology 14: 1169-1176, 1999. In addition, an EGFR antisense-transfected OVCAR 8 ovarian carcinoma line displayed major changes from the vector only control line, leading to the following submission also in June,1999: Alper, O., DeSantis, M.L., Stromberg, K, Hacker, N.F., Cho-Chung, Y.S., and Salomon, D.S.: Epidermal Growth Factor Receptor-Antisense Expressing Ovarian Cancer Cells: Altered Cellular Proliferation, Adhesion Protein Expression and Tumorigenicity. Ovarian carcinoma tissues have also been examined. The particular appeal of ovarian carcinogenesis as a model system is a relatively unusual histologic subtype termed """"""""Borderline Ovarian Tumor"""""""" (BOT), which is a highly proliferative tumor histologically, but one that does not invade adjacent stroma, unlike the customary ovarian carcinoma. Thus, the Borderline Ovarian Tumor (BOT) is ideal as a control to compare what gene products are associated with hyperplasia versus true invasive carcinoma. In contrast to quantitative RT-PCR analysis of two ligands and the four receptors of the erbB family which showed no obvious differential mRNA expression between Stage 1 BOT ovarian carcinomas with Stage 3 invasive ovarian carcinomas, screening for the angiogenesis-associated genes of VEGF and Flt-1 and KDR/Fkt-1 indicated mild to marked elevation in invasive ovarian carcinomas when normalized to a house-keeping gene (Beta-glucoronidas) and when levels were expressed relative to CD31 (an endothelial cell specfic marker gene). Excitingly, however, novel VEGF target genes such as DSCR (Downes Syndrome Critical Region) genes, TLR7 and TLR8, were dramatically overexpressed in invasive ovarian carcinomas compared to BOTs (regression coefficients with a P-values each greater that < 0.0001). We wish to confirm and extent these observations with more tumor samples, as well as normal ovarian surface epithelium, and ovarian carcinoma cell lines NIH:OVCAR-8 and OVCA-429 which have differential angiogenic capacity. Modulation of TLR7 and TLR8 expression by VEGF in vitro represents a novel assessment of what may be initial stages in the angiogenesis process of ovarian carcinomas. We wish therefore to compare and contrast angiogenesis parameters of, for example, matrigel invasion and TLR7 and TLR8 expression, in NIH:OVCAR-8 (low angiogenesis) and OVCA 429 (high angiogenesis) ovarian carcinoma cell lines.
