Epithelial cells are dependent upon adhesion to extracellular matrix for survival. We show that loss of beta 1 integrin receptor contact with extracellular matrix signals the inhibition of G(1) cyclin-dependent kinase activity. This loss of cyclin-dependent kinase activity leads to accumulation of the hypophosphorylated (active) form of the retinoblastoma tumor suppressor protein (Rb). We present evidence that in epithelial cells deprived of matrix contact, the growth suppression signal elicited by hypophosphorylated Rb opposes stimulatory signals hom serum growth factors, leading to a cell cycle conflict that triggers apoptosis. This apoptotic pathway is modulated by Bcl-2 through a novel mechanism that regulates Rb phosphorylation. We present evidence that the Rb-dependent apoptotic pathway functions in vivo in the apoptosis of the prostate glandular epithelium following castration.
机构:
UNIV CALIF SAN FRANCISCO, RADIOBIOL & ENVIRONM HLTH LAB, SAN FRANCISCO, CA 94143 USAUNIV CALIF SAN FRANCISCO, RADIOBIOL & ENVIRONM HLTH LAB, SAN FRANCISCO, CA 94143 USA
BOUDREAU, N
SYMPSON, CJ
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UNIV CALIF SAN FRANCISCO, RADIOBIOL & ENVIRONM HLTH LAB, SAN FRANCISCO, CA 94143 USAUNIV CALIF SAN FRANCISCO, RADIOBIOL & ENVIRONM HLTH LAB, SAN FRANCISCO, CA 94143 USA
SYMPSON, CJ
WERB, Z
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机构:
UNIV CALIF SAN FRANCISCO, RADIOBIOL & ENVIRONM HLTH LAB, SAN FRANCISCO, CA 94143 USAUNIV CALIF SAN FRANCISCO, RADIOBIOL & ENVIRONM HLTH LAB, SAN FRANCISCO, CA 94143 USA
WERB, Z
BISSELL, MJ
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UNIV CALIF SAN FRANCISCO, RADIOBIOL & ENVIRONM HLTH LAB, SAN FRANCISCO, CA 94143 USAUNIV CALIF SAN FRANCISCO, RADIOBIOL & ENVIRONM HLTH LAB, SAN FRANCISCO, CA 94143 USA
机构:
UNIV CALIF SAN FRANCISCO, RADIOBIOL & ENVIRONM HLTH LAB, SAN FRANCISCO, CA 94143 USAUNIV CALIF SAN FRANCISCO, RADIOBIOL & ENVIRONM HLTH LAB, SAN FRANCISCO, CA 94143 USA
BOUDREAU, N
SYMPSON, CJ
论文数: 0引用数: 0
h-index: 0
机构:
UNIV CALIF SAN FRANCISCO, RADIOBIOL & ENVIRONM HLTH LAB, SAN FRANCISCO, CA 94143 USAUNIV CALIF SAN FRANCISCO, RADIOBIOL & ENVIRONM HLTH LAB, SAN FRANCISCO, CA 94143 USA
SYMPSON, CJ
WERB, Z
论文数: 0引用数: 0
h-index: 0
机构:
UNIV CALIF SAN FRANCISCO, RADIOBIOL & ENVIRONM HLTH LAB, SAN FRANCISCO, CA 94143 USAUNIV CALIF SAN FRANCISCO, RADIOBIOL & ENVIRONM HLTH LAB, SAN FRANCISCO, CA 94143 USA
WERB, Z
BISSELL, MJ
论文数: 0引用数: 0
h-index: 0
机构:
UNIV CALIF SAN FRANCISCO, RADIOBIOL & ENVIRONM HLTH LAB, SAN FRANCISCO, CA 94143 USAUNIV CALIF SAN FRANCISCO, RADIOBIOL & ENVIRONM HLTH LAB, SAN FRANCISCO, CA 94143 USA