Journal article
Lysophosphatidic acid stimulates phospholipase D activity and cell proliferation in PC‐3 human prostate cancer cells
Journal of cellular physiology, Vol.174(2), pp.261-272
02/1998
Handle:
https://hdl.handle.net/2376/113654
PMID: 9428812
Abstract
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 EC50 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 EC50 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 Gi‐independent pathways in a human prostate cancer cell line. J. Cell. Physiol. 174:261–272, 1998. © 1998 Wiley‐Liss, Inc.
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Details
- Title
- Lysophosphatidic acid stimulates phospholipase D activity and cell proliferation in PC‐3 human prostate cancer cells
- Creators
- Chen QiJin‐Hyouk ParkTerra C GibbsDavid W ShirleyCynthia D BradshawKrishna M EllaKathryn E Meier
- Publication Details
- Journal of cellular physiology, Vol.174(2), pp.261-272
- Academic Unit
- Pharmaceutical Sciences, Department of
- Publisher
- Wiley Subscription Services, Inc., A Wiley Company; Hoboken
- Number of pages
- 12
- Grant note
- University Research Committee of the Medical University of South Carolina National Institutes of Health (CA58640) National Science Foundation (EPS‐9630167)
- Identifiers
- 99900548089601842
- Language
- English
- Resource Type
- Journal article