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

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Abstract

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.

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Authors and Affiliations

  1. Biochemistry Department, Faculty of Science, King Abdulaziz University, Jeddah, 21589, Kingdom of Saudi Arabia

    Samir F. Zohny, Abdulrahman L. Al-Malki, Mazin A. Zamzami & Hani Choudhry

  2. Biochemistry Department, Faculty of Science, Ain Shams University, Abbassia, 11566, Cairo, Egypt

    Samir F. Zohny

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  1. Samir F. Zohny
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  2. Abdulrahman L. Al-Malki
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Correspondence to Samir F. Zohny.

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Zohny, S.F., Al-Malki, A.L., Zamzami, M.A. et al. p21Waf1/Cip1: its paradoxical effect in the regulation of breast cancer. Breast Cancer 26, 131–137 (2019). https://doi.org/10.1007/s12282-018-0913-1

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  • DOI: https://doi.org/10.1007/s12282-018-0913-1

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