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Effects of Lysophosphatidic Acid on CCN1 Expression in Human Prostate Cancer Cell Lines
Author(s) -
Zhang Zhihong,
Bailey Chrystal R,
Meier Kathryn E
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.758.14
Subject(s) - du145 , lysophosphatidic acid , lncap , cancer research , cancer cell , prostate cancer , autocrine signalling , g protein coupled receptor , gene knockdown , cell growth , microbiology and biotechnology , cell migration , cell , cancer , biology , cell culture , receptor , chemistry , signal transduction , biochemistry , genetics
Lysophosphatidic Acid (LPA) is a lipid growth factor that increases proliferation and migration of prostate cancer cells through the G protein‐coupled receptors (GPCRs) LPA1 and LPA3. CCN1 is an inducible secreted matricellular protein that facilitates adhesion signaling, thereby enhancing cancer cell migration and survival. Knockdown of CCN1 in Du145, PC‐3, and LNCaP cells has been shown to limit proliferation. This study addressed the hypothesis that LPA acts through LPA GPCRs to increase the expression of CCN1 in human prostate cancer cells. The results showed that LPA increases expression of CCN1 protein in Du145 and PC‐3 prostate cancer cell lines, with maximal levels reached by 16 hours (Du145) and 4 hours (PC‐3) respectively. Treatment of Du145 and PC‐3 cells with Ki16425, an LPA antagonist acting at LPA1 and LPA3, blocks LPA‐induced expression of CCN1. Knockdown of LPA1 receptors, using siRNA, results in a decrease in LPA‐induced CCN1 expression. These studies provide the basis for continued studies of the role of CCN1 in prostate cancer cells, and for the development and testing of LPA antagonists as potential therapeutic agents in prostate cancer (Supported by UW Grant Number UL1RR025014 from the National Center for Research Resources).