p21Waf1/Cip1: its paradoxical effect in the regulation of breast cancer

Autor: Mazin A. Zamzami, Abdulrahman L. Al-Malki, Hani Choudhry, Samir F. Zohny
Rok vydání: 2018
Předmět:
Zdroj: Breast Cancer. 26:131-137
ISSN: 1880-4233
1340-6868
DOI: 10.1007/s12282-018-0913-1
Popis: p21Waf1/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 p21Waf1/Cip1 may also function as an oncogene because it can inhibit apoptosis. Thus, p21Waf1/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 p21Waf1/Cip1 expression for therapy of breast cancer patients. This review illustrates the discovery and mechanisms of induction of p21Waf1/Cip1. Then, we focus on elucidating the paradoxical effect of p21Waf1/Cip1 expression on human breast carcinogenesis and explaining how the subcellular localization (nuclear or cytoplasmic) of p21Waf1/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 p21Waf1/Cip1 could affect the responsiveness of human breast cancer to chemotherapy. Furthermore, the pharmacological approaches to target p21Waf1/Cip1 expression for therapy of breast cancer are clarified.
Databáze: OpenAIRE
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