p21: its paradoxical effect in the regulation of breast cancer.

p21, 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 may also function as an oncogene because it can inhibit apoptosis. Thus, p21 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 expression for therapy of breast cancer patients. This review illustrates the discovery and mechanisms of induction of p21. Then, we focus on elucidating the paradoxical effect of p21 expression on human breast carcinogenesis and explaining how the subcellular localization (nuclear or cytoplasmic) of p21 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 could affect the responsiveness of human breast cancer to chemotherapy. Furthermore, the pharmacological approaches to target p21 expression for therapy of breast cancer are clarified.