Gartel Andrei L, Tyner Angela L
Department of Molecular Genetics, University of Illinois College of Medicine, Chicago, Illinois 60607, USA.
Mol Cancer Ther. 2002 Jun;1(8):639-49.
Cancer develops when the balance between cell proliferation and cell death is disrupted, and the ensuing aberrant proliferation leads to tumor growth. The cyclin-dependent kinase inhibitor p21 is induced by both p53-dependent and -independent mechanisms following stress, and induction of p21 may cause cell cycle arrest. As a proliferation inhibitor, p21 is poised to play an important role in preventing tumor development. This notion is supported by data indicating that p21-null mice are more prone to spontaneous and induced tumorigenesis, and p21 synergizes with other tumor suppressors to protect against tumor progression in mice. However, a number of recent studies have pointed out that in addition to being an inhibitor of cell proliferation, p21 acts as an inhibitor of apoptosis in a number of systems, and this may counteract its tumor-suppressive functions as a growth inhibitor. In the current review, we discuss the role of p21 in regulating cell death and the potential relevance of its expression in cancer.
当细胞增殖与细胞死亡之间的平衡被打破时，癌症就会发生，随之而来的异常增殖会导致肿瘤生长。细胞周期蛋白依赖性激酶抑制剂p21在应激后通过p53依赖性和非依赖性机制被诱导，p21的诱导可能导致细胞周期停滞。作为一种增殖抑制剂，p21有望在预防肿瘤发生中发挥重要作用。这一观点得到了以下数据的支持：即p21基因缺失的小鼠更容易发生自发和诱导性肿瘤发生，并且p21与其他肿瘤抑制因子协同作用以保护小鼠免受肿瘤进展。然而，最近的一些研究指出，除了作为细胞增殖的抑制剂外，p21在许多系统中还作为细胞凋亡的抑制剂起作用，这可能会抵消其作为生长抑制剂的肿瘤抑制功能。在当前的综述中，我们讨论了p21在调节细胞死亡中的作用及其在癌症中表达的潜在相关性。
