Cancer Research Infection and Cancer: Biology, Therapeutics, and Prevention Susan G. Komen for the Cure-AACR Outstanding Investigator Award for Breast Cancer Research
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[Cancer Research 62, 2227-2231, April 15, 2002]
© 2002 American Association for Cancer Research

Advances in Brief

Cholesterol-rich Lipid Rafts Mediate Akt-regulated Survival in Prostate Cancer Cells1

Liyan Zhuang2, Jianqing Lin2, Michael L. Lu, Keith R. Solomon3 and Michael R. Freeman3,4

The Urologic Laboratory, Department of Urology [L. Z., J. L., M. R. F.], and the Department of Orthopaedic Surgery, Children’s Hospital [K. R. S.], Division of Urologic Surgery, Brigham and Women’s Hospital [M. L. L.], and the Department of Surgery, Harvard Medical School [L. Z., J. L., M. L. L., K. R. S., M. R. F.], Boston, Massachusetts 02115

Although cholesterol accumulation in tumors was first reported in the early20th century, the mechanistic implications of this observation are stillobscure. Here we report that caveolin-negative human prostate cancer (LNCaP) cells contain cholesterol-rich lipid rafts that mediate epidermal growth factor (EGF)-induced and constitutive signaling through the Akt1 serine-threonine kinase. EGF receptor and Akt1 phosphorylation were inhibited and autonomous cell survival was reduced when the rafts were disrupted. Reconstitution of the rafts with cholesterol restored EGF receptor->Akt1 axis signaling and cytoprotection from a phosphoinositide 3-kinase-dependent apoptotic signal. These results suggest that cholesterol present in membrane microdomains is a prominent mediator of survival in prostate cancer cells.




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Copyright © 2002 by the American Association for Cancer Research.