Details

Autor(en) / Beteiligte

• Heasley, L E
• Thaler, S
• Nicks, M
• Price, B
• Skorecki, K
• Nemenoff, R A

Titel

Induction of Cytosolic Phospholipase A2 by Oncogenic Ras in Human Non-small Cell Lung Cancer

Ist Teil von

• The Journal of biological chemistry, 1997-06, Vol.272 (23), p.14501-14504

Ort / Verlag

United States: American Society for Biochemistry and Molecular Biology

Erscheinungsjahr

1997

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 E 2 (PGE 2 ) compared with NSCLC lacking Ras mutations or non-transformed lung epithelial cells (BEAS-2B). This increased PGE 2 production was mediated by constitutively high expression of 85-kDa cytosolic phospholipase A 2 (cPLA 2 ) and cyclooxygenase 2 (COX-2). The increased expression of cPLA 2 protein was mediated through elevated mRNA levels and activation of the cPLA 2 promoter. Induction of cPLA 2 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 cPLA 2 and COX-2. Finally, inhibitors of eicosanoid synthesis blocked anchorage-independent growth of NSCLC lines exhibiting Ki-Ras mutations. These results identify cPLA 2 as a novel Ras-inducible regulator of eicosanoid synthesis that participates in cellular transformation.