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Lysophosphatidic acid stimulates phospholipase D activity and cell proliferation in PC‐3 human prostate cancer cells
Author(s) -
Qi Chen,
Park JinHyouk,
Gibbs Terra C.,
Shirley David W.,
Bradshaw Cynthia D.,
Ella Krishna M.,
Meier Kathryn E.
Publication year - 1998
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/(sici)1097-4652(199802)174:2<261::aid-jcp13>3.0.co;2-f
Subject(s) - lysophosphatidic acid , prostate cancer , cell growth , phospholipase d , cancer , cancer cell , cancer research , cell , microbiology and biotechnology , biology , chemistry , medicine , biochemistry , signal transduction , receptor
Phospholipase D (PLD) is activated in mammalian cells in response to a variety of growth factors and may play a role in cell proliferation. Lysophosphatidic acid (LPA) is a bioactive metabolite potentially generated as a result of PLD activation. Two human prostate cancer cell lines, PC‐3 and LNCaP, express membrane PLD activity. The effects of LPA on PLD activity and proliferation were examined in PC‐3 cells, which express hPLD1a/1b. Phorbol 12‐myristate 13‐acetate (PMA) induced a prolonged activation of PLD, as detected in both intact cells and membranes. LPA induced a transient activation of PLD that was maximal by 10 minutes. The EC 50 for LPA‐induced PLD activation was approximately 1 μM. Pertussis toxin did not inhibit activation of PLD by LPA or PMA. Ro‐31‐8220 and bisindolylmaleimide I, inhibitors of protein kinase C, blocked activation by PLD by both PMA and LPA. PMA‐induced activation of PLD did not appear to require translocation of PLDs from cytosol to membrane. LPA stimulated proliferation of PC‐3 cells with an EC 50 of approximately 0.2 μM; this response was not inhibited by pertussis toxin. Perillyl alcohol, an anti‐cancer drug, reversibly inhibited proliferation in response to either serum or LPA but did not inhibit activation of PLD by PMA or LPA. These data establish that LPA activates PLD and stimulates proliferation via G i ‐independent pathways in a human prostate cancer cell line. J. Cell. Physiol. 174:261–272, 1998. © 1998 Wiley‐Liss, Inc.