This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Pidgeon, G. P. Articles by Honn, K. V. Search for Related Content PubMed PubMed Citation Articles by Pidgeon, G. P. Articles by Honn, K. V.

Overexpression of Platelet-type 12-Lipoxygenase Promotes Tumor Cell Survival by Enhancing _vß₃ and _vß₅ Integrin Expression¹

Departments of Radiation Oncology [G. P. P., K. T., Y. L. C., K. V. H.], Pathology [K. V. H.], and Medicine [E. P.], Wayne State University, Detroit, Michigan 48202, and Karmanos Cancer Institute, Detroit, Michigan 48201 [K. V. H.]

Arachidonic acid metabolism leads to the generation of biologically active metabolites that regulate cell growth and proliferation, as well as survival and apoptosis. We have demonstrated previously that platelet-type 12-lipoxygenase (LOX) regulates the growth and survival of a number of cancer cells. In this study, we show that overexpression of platelet-type 12-LOX in prostate cancer PC3 cells or epithelial cancer A431 cells significantly extended their survival and delayed apoptosis when cultured under serum-free conditions. These effects were shown to be a result of enhanced surface integrin expression, resulting in a more spread morphology of the cells in culture. PC3 cells transfected with 12-LOX displayed increased _vß₃ and _vß₅ integrin expression, whereas other integrins were unaltered. Transfected A431 cells did not express _vß₃; however, _vß₅ integrin expression was increased. Treatment of both transfected cell lines with monoclonal antibody to _vß₅ (and in the case of PC3 cells, anti-_vß₃) resulted in significant apoptosis. In addition, treatment with 100 nM 12(S)-hydroxy-eicosatetraenoic acid, the end product of platelet-type 12-LOX, but not other hydroxy-eicosatetraenoic acids, enhanced the survival of wild-type PC3 and A431 cells and resulted in increased expression of _vß₅. Furthermore, Baicalein or N-benzyl-N-hydroxy-5-phenylpentamide, specific 12-LOX inhibitors, significantly decreased _vß₅-mediated adhesion and survival in 12-LOX-overexpressing cells. The results show that 12-LOX regulates cell survival and apoptosis by affecting the expression and localization of the vitronectin receptors, _vß₃ and _vß₅, in two cancer cell lines.

This article has been cited by other articles:

				M. W. Buczynski, D. S. Dumlao, and E. A. Dennis Thematic Review Series: Proteomics. An integrated omics analysis of eicosanoid biology J. Lipid Res., June 1, 2009; 50(6): 1015 - 1038. [Abstract] [Full Text] [PDF]

				Y.-S. Piao, Y.-C. Du, H. Oshima, J.-C. Jin, M. Nomura, T. Yoshimoto, and M. Oshima Platelet-type 12-lipoxygenase accelerates tumor promotion of mouse epidermal cells through enhancement of cloning efficiency Carcinogenesis, February 1, 2008; 29(2): 440 - 447. [Abstract] [Full Text] [PDF]

				S. Chouinard, G. Pelletier, A. Belanger, and O. Barbier Isoform-Specific Regulation of Uridine Diphosphate-Glucuronosyltransferase 2B Enzymes in the Human Prostate: Differential Consequences for Androgen and Bioactive Lipid Inactivation Endocrinology, November 1, 2006; 147(11): 5431 - 5442. [Abstract] [Full Text] [PDF]

				M. P. Abbracchio, G. Burnstock, J.-M. Boeynaems, E. A. Barnard, J. L. Boyer, C. Kennedy, G. E. Knight, M. Fumagalli, C. Gachet, K. A. Jacobson, et al. International Union of Pharmacology LVIII: Update on the P2Y G Protein-Coupled Nucleotide Receptors: From Molecular Mechanisms and Pathophysiology to Therapy Pharmacol. Rev., September 1, 2006; 58(3): 281 - 341. [Abstract] [Full Text] [PDF]

				D. Nie, S. Krishnamoorthy, R. Jin, K. Tang, Y. Chen, Y. Qiao, A. Zacharek, Y. Guo, J. Milanini, G. Pages, et al. Mechanisms Regulating Tumor Angiogenesis by 12-Lipoxygenase in Prostate Cancer Cells J. Biol. Chem., July 7, 2006; 281(27): 18601 - 18609. [Abstract] [Full Text] [PDF]

				M. Edderkaoui, P. Hong, E. C. Vaquero, J. K. Lee, L. Fischer, H. Friess, M. W. Buchler, M. M. Lerch, S. J. Pandol, and A. S. Gukovskaya Extracellular matrix stimulates reactive oxygen species production and increases pancreatic cancer cell survival through 5-lipoxygenase and NADPH oxidase Am J Physiol Gastrointest Liver Physiol, December 1, 2005; 289(6): G1137 - G1147. [Abstract] [Full Text] [PDF]

				M. F. McCarty Targeting Multiple Signaling Pathways as a Strategy for Managing Prostate Cancer: Multifocal Signal Modulation Therapy Integr Cancer Ther, December 1, 2004; 3(4): 349 - 380. [Abstract] [PDF]

				M. J. Coffey, G. E. Jarvis, J. M. Gibbins, B. Coles, N. E. Barrett, O. R.E. Wylie, and V. B. O'Donnell Platelet 12-Lipoxygenase Activation via Glycoprotein VI: Involvement of Multiple Signaling Pathways in Agonist Control of H(P)ETE Synthesis Circ. Res., June 25, 2004; 94(12): 1598 - 1605. [Abstract] [Full Text] [PDF]