P29. Regulation of TGF-β1 in intercellular junctions in epithelial ovarian carcinomas

Abstract

Epithelial ovarian cancer (EOC) commonly thought to arise from ovarian surface epithelia (OSE) covering the ovaries is the fifth most common cause of cancer related death in females in the Western world. It is the most lethal form of all gynecological malignancy due to the diagnosis at late stages. The pathogenesis of EOC and mechanisms underlying this event remain poorly defined. Epithelial–mesenchymal transition (EMT), a process with loss of polarity and disruption of intercellular junctions, is vital for embryonic morphogenesis as well as cancer metastasis. We have shown that TGF-β1 can induce EMT in OSE in vitro . In this study, we investigated whether TGF-β1 induces EMT in the cultured ovarian cancer cell line, OVCAR-3. We studied phenotype and trans-epithelial resistance in a filter culture insert system. Regulation of TGF-β1 in cell–cell adhesion was examined by analyzing the expression of tight junction proteins, occludin, claudin-1, -3, -4 and -7, and adherens junction proteins N-cadherin and E-cadherin using Western blotting and their mRNA expression by qPCR. We did not observe any cell phenotypic difference between TGF-β1 treated and untreated OVCAR-3. However, we did find a decrease of trans-epithelial resistance in TGF-β1 treated cells concomitant with downregulated protein and/or RNA expressions of E-cadherin, occludin as well as claudin-3, and -4, -7 whereas upregulated N-cadherin and claudin 1 in TGF-β1 treated cells. Our results suggest that TGF-β1 can modulate the formation of tight junction and adherens junction and the ion-barrier function of tight junction in OVCAR-3 without transition to a mesenchymal phenotype.