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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Cell Membrane / metabolism
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Cell Survival / physiology
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Cholesterol / metabolism
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Cholesterol / physiology*
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Epidermal Growth Factor / pharmacology
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ErbB Receptors / physiology
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Humans
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Male
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Membrane Lipids / metabolism
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Membrane Lipids / pharmacology
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Phosphatidylinositol 3-Kinases / metabolism
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Phosphatidylinositol 3-Kinases / physiology
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Prostatic Neoplasms / enzymology
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Prostatic Neoplasms / metabolism*
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Prostatic Neoplasms / pathology*
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Protein Serine-Threonine Kinases*
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins / physiology*
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Proto-Oncogene Proteins c-akt
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Recombinant Proteins / pharmacology
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Signal Transduction / physiology
Substances
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Membrane Lipids
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Proto-Oncogene Proteins
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Recombinant Proteins
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Epidermal Growth Factor
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Cholesterol
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ErbB Receptors
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AKT1 protein, human
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt