Induction of cytosolic phospholipase A2 by oncogenic Ras in human non- small cell lung cancer

Lynn E. Heasley, Seth Thaler, Michael Nicks, Brenda Price, Karl Skorecki, Raphael A. Nemenoff

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163 Scopus citations


Mutations in Ras family members that confer oncogenic potential are frequently observed in specific human cancers. We report that human non- small cell lung cancer (NSCLC) lines that harbor oncogenic mutations in Ki- Ras (H460, A549, H2122) synthesized high levels of prostaglandin E2 (PGE2) compared with NSCLC lacking Ras mutations or non-transformed lung epithelial cells (BEAS-2B). This increased PGE2 production was mediated by constitutively high expression of 85-kDa cytosolic phospholipase A2 (cPLA2) and cyclooxygenase 2 (COX-2). The increased expression of cPLA2 protein was mediated through elevated mRNA levels and activation of the cPLA2 promoter. Induction of cPLA2 promoter activity was blocked by expression of dominant- negative forms of Ras. Inhibition of Ras by the farnesyltransferase inhibitor BZA-5B inhibited prostaglandin synthesis in H2122 cells by decreasing expression of both cPLA2 and COX-2. Finally, inhibitors of eicosanoid synthesis blocked anchorage-independent growth of NSCLC lines exhibiting Ki- Ras mutations. These results identify cPLA2 as a novel Ras-inducible regulator of eicosanoid synthesis that participates in cellular transformation.

Original languageEnglish
Pages (from-to)14501-14504
Number of pages4
JournalJournal of Biological Chemistry
Issue number23
StatePublished - 6 Jun 1997
Externally publishedYes


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