15-Lipoxygenase-1 Overexpression in Prostate Adenocarcinoma

  • Uddhav Kelavkar
  • Cynthia Cohen
  • Thomas Eling
  • Kamal Badr
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 507)


Arachidonate 15-lipoxygenase[15-LO-1]oxidizes linoleic acid, arachidonic acid, membrane lipids and low density lipoprotein, reactions of potential relevance to inflammation, membrane remodeling, atherosclerosis ’ and cancer. The oxidation products of one of its substrates, linoleic acid (LA), are involved in the regulation of both physiologic and pathologic processes2-7. The major oxidative metabolite of LA is the hydroxy fatty acid 13-hydroxyoctadecadienoic acid (13-(S)-HODE) which has been associated with proliferative processes in response to growth factor treatment3.7. Buchanan et al.3have shown that tumor cell adhesivity is dependent, in part, upon the relative amounts of intracellular 13-HODE and the arachidonic acid monohydroxide(s), 12- and/or 15-hydroxyeicosatetraenoic acids (12-, 15-HETE). Arachidonic acid (AA) metabolites are similarly important mediators of a variety of physiologic processes and inflammatory reactions, including neoplastic processes8. AA is metabolized via cyclooxygenase to prostaglandins, prostacyclin, and thromboxane9and via lipoxygenases (LO) to hydroxyeicosatetraenoic acids (HETEs), leukotrienes and lipoxins (5 and15-LOpathways) ’. Four lipoxygenases are identified in humans: a 5S-LO found in leukocytes, a 12S-LO and 12R-LO found in platelets and certain epithelia, a15-LO-1in reticulocytes, eosinophils, macrophages, prostate, liver, kidney, spleen, thymus, testis, ovary, skeletal muscle, heart, brain, or intestinal tissue (Table 1) and 15-S-lipoxygenase(15-LO-2)found predominantly in benign prostate and skin10. The15-LO-1cDNA was cloned from a human reticulocyte cDNA library “ and is found in a variety of tissues, mainly of epithelial origin (Table 1).


High Performance Liquid Chromatography Linoleic Acid Arachidonic Acid Seminal Vesicle High Performance Liquid Chromatography Analysis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. l.
    Samuelsson, B., Dehien, S.E., Lindgren, J.A., Rouzer, C.A. and Serhan, C.N. (1987) Science. 237: 1171–1176.PubMedCrossRefGoogle Scholar
  2. 2.
    Bertomeu, M.C., Gallo, S., Lauri, D., Haas, T.A., Orr, F.W., Bastida, E. and Buchanan, M.R. Clin. Exp. Metastasis. 11: 243–250 (1993).CrossRefGoogle Scholar
  3. 3.
    Buchanan, M.R., Horsewood, P. and Brister, S.J. Prostaglandins Leukot. Essent. Fatty Acids. 58: 339–346 (1998).CrossRefGoogle Scholar
  4. 4.
    Ikawa, H., Kamitani, H., Calvo, B.F., Foley, J.F. and Eling, T.E. Cancer Res., 59: 360–366 (1999).PubMedGoogle Scholar
  5. 5.
    Kamitani, H., Geller, M. and Eling, T. J. Biol. Chem., 273, 21569–21577 (1998).CrossRefGoogle Scholar
  6. 6.
    Natarajan, R. and Nadler, J. Front. Biosci. 3: E81–88 (1998).PubMedGoogle Scholar
  7. 7.
    Reddy, N., Everhart, A., Eling, T. and Glasgow, W. Biochem. Biophys Res. Commun. 231: 111–116 (`97).Google Scholar
  8. 8.
    Marnett, U. Cancer Res. 52: 5575–5589 (1992).Google Scholar
  9. 9.
    Smith, W.L., Garavito, R.M. and DeWitt, D.L.J.Biol.Chem.271: 33157–33160 (1996).CrossRefGoogle Scholar
  10. 10.
    Brash, A.R., Boeglin, W.E. and Chang, M.S. Proc. Natl. Acad. Sci. USA. 94: 6146–6152 (1997).CrossRefGoogle Scholar
  11. 11.
    Sigal, E., Craik, C.S., Highland, E., Grunberger, D.,Costello, L.L.,Dixon, R.A. and Nadel, J.A. Biochem. Biophys. Res. Commun. 157: 457–464 (1998).Google Scholar
  12. 12.
    Spindler, S.A., Sarkar, F.H., Sakr, W.A., Blackburn, M.L., Bull, A.W., LaGattuta, M. and Reddy, R.G. Biochem. Biophys. Res. Commun. 239: 775–781 (1997).Google Scholar
  13. 13.
    Nadel, J.A., Conrad, D.J., Ueki, I.F., Schuster, A. and Sigal, E. J. Clin. Invest. 87: 1139–1145 (1991).CrossRefGoogle Scholar
  14. 14.
    Lei, Z.M. and Rao, C.V. Endocrinology., 130: 861–870 (1992).PubMedGoogle Scholar
  15. 15.
    Kirkegaard, L.J., DeRose, P.B., Yao, B. and Cohen, C. Am. J. Clin. Pathol. 109: 69–74 (1998).Google Scholar
  16. 16.
    Cohen, C. and DeRose, P.B. Mod. Pathol. 7: 536–539 (1994).PubMedGoogle Scholar
  17. 17.
    Goel, A., Abou-Ella, A., DeRose, P. and Cohen, C. J. Urol. Path.4: 213–225 (1996).Google Scholar
  18. 18.
    Shappell, S.B., Boeglin, W.E., Olson, S.J., Kasper, S. and Brash, A.R. Am. J. Pathol. 155: 235–245 (`99).Google Scholar
  19. 19.
    Kelavkar, U. P., Wang, S. and Badr, K. F. Genes and Immunity. (In press) (2000).Google Scholar
  20. 20.
    Chomarat, P. and Banchereau, J. Int. Rev. Immunol. 17: 1–52 (1998).CrossRefGoogle Scholar
  21. 21.
    Deleuran, B., Iversen, L., Deleuran, M., Yssel, H., Kragballe, K., Stengaard-Pedersen K. and ThestrupPedersen, K. Cytokine. 7: 319–324 (1995).PubMedCrossRefGoogle Scholar
  22. 22.
    Maini, A., Hillman, G., Haas, G.P., Wang, C.Y., Montecillo, E., Hamzavi, F., Pontes, J.E., Leland, P., Pastan, I., Debinski, W. and Puri, R.K. J. Urol. 158: 948–953 (1997).PubMedCrossRefGoogle Scholar
  23. 23.
    Nassar, G.M., Morrow, J.D., Roberts, L.J., Lakkis, F.G., Badr, K.F. J. Biol. Chem. 269: 27631–27634 (1994).Google Scholar
  24. 24.
    Kelavkar, U.P. and Badr, K.F. Proc. Natl. Acad. Sci. USA. 96: 4378–4383 (1999).CrossRefGoogle Scholar
  25. 25.
    Cheng, L., Leibovich, B.C., Bergstralh, E.J., Scherer, B.G., Pacelli, A., Ramnani, D.M., Zincke, H. and Bostwick, D.G. Cancer. 85: 2455–2459 (1999).PubMedCrossRefGoogle Scholar
  26. 26.
    Gurnani, M., Lipari, P., Dell, J., Shi, B. and Nielsen, L.L. Cancer Chemother. Pharmacol. 44: 143–151 (1999).Google Scholar
  27. 27.
    Chaudry, A.A., Wahie, K.W.J., MoClinton, S. and Moffat, L.E.F. Int. J.Cancer. 57: 176–180 (1994).Google Scholar
  28. 28.
    Gao, X., Grignon, D.J., Chbihi, T., Zacharek, A., Chen, Y.O., Sakr, W., Porter, A.T., Crissman, J.D., Pontes, J.E., Powell, I.J. and Honn, K.V. Urology. 46: 227–237 (1995).PubMedCrossRefGoogle Scholar
  29. 29.
    Ghosh, J and Myers, C.E. Biochem. Biophys. Res. Commun. 235: 418–423 (1997).Google Scholar
  30. 30.
    Glasgow, W.C. and Everhart, A.L. Adv. Exp. Med. Biol., 407: 393–397 (1997).Google Scholar
  31. 31.
    Blask, D.E., Sauer, L.A., Dauchy, R., Holowachuk, E.W. and Ruhoff, M.S. Biol. Signals Recept., 8: 49–55 (1999).PubMedCrossRefGoogle Scholar
  32. 32.
    Banni, S., Angioni, E., Casu, V., Melis, M.P., Carta, G., Corongiu, F.P., Thompson, H. and Ip C. Carcinogenesis. 20: 1019–1024 (1999).PubMedCrossRefGoogle Scholar
  33. 33.
    Rose, D.P. and Connolly, J.M. Int. J. Oncol. 13: 1179–1183 (1998).Google Scholar
  34. 34.
    Sauer, L.A., Dauchy, R.T., Blask, D.E., Armstrong, B.J. and Scalici, S. Cancer Res. 59: 4688–4692 (1999).PubMedGoogle Scholar
  35. 35.
    Connolly, J.M., Gilhooly, E.M. and Rose, D.P. Nutr. Cancer. 35: 44–49 (1999).PubMedCrossRefGoogle Scholar
  36. 36.
    Liu, X.H., Connolly, J.M. and Rose, D.P. Clin.Exp. Metastasis. 14: 145–152 (1996).CrossRefGoogle Scholar
  37. 37.
    Rose, D.P. and Connolly, J.M. Prostate. 18: 243–254 (1991).Google Scholar
  38. 38.
    Connolly, J.M., Coleman, M. and Rose, D.P. Nutr. Cancer. 29: 114–119 (1997).PubMedCrossRefGoogle Scholar
  39. 39.
    Cesano, A., Visonneau, S., Scimeca, J.A., Kritchevsky, D. and Santoli, D. Anticancer Res. 18: 1429–1434 (1998).PubMedGoogle Scholar
  40. 40.
    Giovannucci, E., Rimm, E.B., Colditz, G.A., Stampfer, M.J., Ascherio, A., Chute, C.C. and Willett, W.C. J. Natl. Cancerbist. 85: 1571–1579 (1993).CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Uddhav Kelavkar
    • 1
  • Cynthia Cohen
    • 2
  • Thomas Eling
    • 3
  • Kamal Badr
    • 1
  1. 1.The Center for Glomerulonephritis, Renal DivisionEmory University and the VAMCAtlanta
  2. 2.Department of PathologyEmory UniversityAtlanta
  3. 3.Laboratory of Molecular Carcinogenesis, NIEHSResearch Triangle Park

Personalised recommendations