Ovarian Cancer Research Today is a free monthly online journal that collates and summarizes the latest research about Ovarian Cancer, including details on symptoms, causes, treatment, information. | ||||||||
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IL-12 receptor-mediated upregulation of FasL in human ovarian carcinoma cells.Gorelik E, Edwards RP, Feng X, Marrangoni AM, Grandis JR, Drenning SD, Velikokhatnaya L, Kwon JA, Lokshin AE Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA. The expression and functions of IL-12 receptor (IL-12R) in human ovarian carcinoma cell lines have been investigated. Ovarian carcinoma cells express both the IL-12Rbeta1 and the IL-12Rbeta2 subunits. IL-12R crosslinking resulted in phosphorylation of Tyk2, p44 (ERK1) and Akt kinases and activation of STATs 2, 3, 4 and 5. IL-12 induced substantial upregulation of Fas ligand (FasL) surface expression in ovarian carcinoma cells paralleled by an increased ability to induce apoptosis in Jurkat cells and PHA-activated lymphocytes. The induction of surface expression of FasL by IL-12 was not due to upregulation of FasL gene expression, but resulted from downregulation of matrix metalloproteinases (MMPs)-3 and -7 and consequently reduced cleavage of FasL from the cell surface. These findings bring new insights into the significance of IL-12-mediated effects in nonlymphoid cancer cells that might be of importance for improving the design of IL-12-based therapies for ovarian cancer. Published 21 September 2004 in Int J Cancer, 112(4): 620-7.
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