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IL-12 receptor-mediated upregulation of FasL in human ovarian carcinoma cells

✍ Scribed by Elieser Gorelik; Robert P. Edwards; Xin Feng; Adele M. Marrangoni; Jennifer R. Grandis; Stephanie D. Drenning; Lyudmila Velikokhatnaya; Jeong-Ah Kwon; Anna E. Lokshin

Publisher: John Wiley and Sons
Year: 2004
Tongue: French
Weight: 299 KB
Volume: 112
Category: Article
ISSN: 0020-7136
DOI: 10.1002/ijc.20482

No coin nor oath required. For personal study only.

✦ Synopsis

Abstract

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‐12Rβ1 and the IL‐12Rβ2 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. © 2004 Wiley‐Liss, Inc.

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