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• W2115344392 abstract "Purpose: Cytosolic phospholipase A2-a (cPLA2-a) provides intracellular arachidonic acid to supply both cyclooxygenase and lipoxygenase pathways. We aim to determine the expression and activation of cPLA2-a in prostate cancer cell lines and tissue and the effect of targeting cPLA2-a in vitro and in vivo. Experimental Design: The expression of cPLA2-a was determined in prostate cancer cells by reverse transcription-PCR,Western blot, and immunocytochemistry. Growth inhibition, apoptosis, and cPLA2-a activity were determined after inhibition with cPLA2-a small interfering RNA or inhibitor (Wyeth-1). Cytosolic PLA2-a inhibitor or vehicle was also administered to prostate cancer xenograft mouse models. Finally, the expression of phosphorylated cPLA2-a was deter- mined by immunohistochemistry in human normal, androgen-sensitive and androgen-insensitive prostate cancer specimens. Results: cPLA2-a is present in all prostate cancer cells lines, but increased in androgen-insensi- tive cells. Inhibition with small interfering RNA or Wyeth-1results in significant reductions in pros- tate cancer cell numbers, as a result of reduced proliferation as well as increased apoptosis, and this was also associated with a reduction in cPLA2-a activity. Expression of cyclin D1and phos- phorylation of Akt were also observed to decrease. Wyeth-1inhibited PC3 xenograft growth by f33% and again, also reduced cyclin D1. Immunohistochemistry of human prostate tissue revealed that phosphorylated cPLA2-a is increased when hormone refractory is reached. Conclusions: Expression and activation of cPLA2-a are increased in the androgen-insensitive cancer cell line and tissue. Inhibition of cPLA2-a results in cells and xenograft tumor growth inhi- bition and serves as a potentially effective therapy for hormone refractory prostate cancer." @default.
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• W2115344392 date "2008-01-01" @default.
• W2115344392 modified "2023-09-22" @default.
• W2115344392 title "Cytosolic Phospholipase A2-A: A Potential TherapeuticTarget for Prostate Cancer" @default.
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