期刊
BREAST CANCER
卷 26, 期 2, 页码 131-137出版社
SPRINGER JAPAN KK
DOI: 10.1007/s12282-018-0913-1
关键词
p21(Waf1/Cip1); p53; Prognosis; Pharmacological approaches; Breast cancer
p21(Waf1/Cip1), the cyclin-dependent kinase (CDK) inhibitor belonging to the KIP/CIP family, was initially regarded as a tumor suppressor protein because it was recognized as the chief mediator of p53-dependent cell cycle arrest elicited by DNA damage. Conversely, it has been proposed that p21(Waf1/Cip1) may also function as an oncogene because it can inhibit apoptosis. Thus, p21(Waf1/Cip1) is regarded as a protein with a dual behavior, as its expression might cause potential benefits or dangerous effects in breast cancer. Consequently, careful planning is required in targeting p21(Waf1/Cip1) expression for therapy of breast cancer patients. This review illustrates the discovery and mechanisms of induction of p21(Waf1/Cip1). Then, we focus on elucidating the paradoxical effect of p21(Waf1/Cip1) expression on human breast carcinogenesis and explaining how the subcellular localization (nuclear or cytoplasmic) of p21(Waf1/Cip1) has an impact on both determining its fate as either cell-growth inhibitor or antiapoptotic molecule and, its effect on clinicopathological factors and prognosis of breast cancer patients. Moreover, we explore how the pattern of the p21(Waf1/Cip1) could affect the responsiveness of human breast cancer to chemotherapy. Furthermore, the pharmacological approaches to target p21(Waf1/Cip1) expression for therapy of breast cancer are clarified.
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