RT Journal Article SR Electronic T1 20-HETE-producing Enzymes Are Up-regulated in Human Cancers JF Cancer Genomics - Proteomics JO Cancer Genomics Proteomics FD International Institute of Anticancer Research SP 163 OP 169 VO 9 IS 4 A1 ANNA ALEXANIAN A1 BRADLEY MILLER A1 RICHARD J. ROMAN A1 ANDREY SOROKIN YR 2012 UL http://cgp.iiarjournals.org/content/9/4/163.abstract AB Background: 20-Hydroxyeicosatetraenoic acid (20-HETE), a metabolite of arachidonic acid (AA) produced by the CYP4A and CYP4F enzyme families has been reported to induce mitogenic and angiogenic responses both in vitro and in vivo, and inhibitors of this pathway reduced growth of brain and kidney tumors. Materials and Methods: Real-Time PCR, western blot and immunohistochemistry were used to compare the expression of CYP4A/F mRNA and protein levels in human cancer tissue samples versus normal controls. Liquid chromatography/mass spectrometry analysis (LC-MS/MS) was performed to measure 20-HETE formation in tumor homogenates. Activation of Ras in human proximal tubule epithelial cells (HRPTEC) treated with stable agonist of 20-HETE was measured using a Ras pull-down detection kit. Results: The expression of CYP4A/4F genes was markedly elevated in thyroid, breast, colon, and ovarian cancer samples in comparison to matched normal tissues. Furthermore, the levels of the CYP4F2 protein and of 20-HETE were higher in ovarian cancer samples compared to normal control tissues. A stable 20-HETE agonist induced activation of the small-GTPase Ras in HRPTEC cells. Conclusion: The present finding of elevated expression of CYP4A/F enzymes in human cancer tissue suggests that 20-HETE inhibitors and antagonists may be useful in the treatment of cancer.