title: Cholesterol-rich lipid rafts mediate akt-regulated survival in prostate cancer cells.
abstract: Although cholesterol accumulation in tumors was first reported in the early20th century, the mechanistic implications of this observation are still obscure. 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.
authors.affiliation: The Urologic Laboratory, Department of Urology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Liyan
authors.initials: L
authors.lastname: Zhuang
authors.forename: Jianqing
authors.initials: J
authors.lastname: Lin
authors.forename: Michael L
authors.initials: ML
authors.lastname: Lu
authors.forename: Keith R
authors.initials: KR
authors.lastname: Solomon
authors.forename: Michael R
authors.initials: MR
authors.lastname: Freeman
mesh_terms: D002462:Cell Membrane / Q000378:metabolism; D002470:Cell Survival / Q000502:physiology; D002784:Cholesterol / Q000378:metabolism / Q000502:physiology*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000502:physiology; D006801:Humans; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism / Q000502:physiology; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology
chemical_list: D002784:Cholesterol; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D008563:Membrane Lipids; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D011994:Recombinant Proteins; C494918:AKT1 protein, human