Day M L, Foster R G, Day K C, Zhao X, Humphrey P, Swanson P, Postigo A A, Zhang S H, Dean D C
Department of Surgery, Division of Urology, and the University of Michigan Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan 48109, USA.
J Biol Chem. 1997 Mar 28;272(13):8125-8. doi: 10.1074/jbc.272.13.8125.
Epithelial cells are dependent upon adhesion to extracellular matrix for survival. We show that loss of beta1 integrin receptor contact with extracellular matrix signals the inhibition of G1 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 from 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.
上皮细胞依赖于与细胞外基质的黏附来维持生存。我们发现，β1整合素受体与细胞外基质失去接触会发出抑制G1期细胞周期蛋白依赖性激酶活性的信号。细胞周期蛋白依赖性激酶活性的丧失导致视网膜母细胞瘤肿瘤抑制蛋白（Rb）的低磷酸化（活性）形式积累。我们提供的证据表明，在缺乏基质接触的上皮细胞中，低磷酸化Rb引发的生长抑制信号与血清生长因子的刺激信号相互拮抗，导致细胞周期冲突，进而引发细胞凋亡。这条凋亡途径由Bcl-2通过一种调节Rb磷酸化的新机制进行调控。我们提供的证据表明，Rb依赖性凋亡途径在去势后前列腺腺上皮细胞凋亡的体内过程中发挥作用。
