Biochemistry Department, Faculty of Science, King Abdulaziz University, Jeddah, 21589, Kingdom of Saudi Arabia.
Biochemistry Department, Faculty of Science, Ain Shams University, Abbassia, 11566, Cairo, Egypt.
Breast Cancer. 2019 Mar;26(2):131-137. doi: 10.1007/s12282-018-0913-1. Epub 2018 Sep 25.
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.
p21 是细胞周期蛋白依赖性激酶（CDK）抑制剂，属于 KIP/CIP 家族，最初被认为是一种肿瘤抑制蛋白，因为它被认为是 p53 依赖性细胞周期阻滞的主要介质，这种阻滞是由 DNA 损伤引起的。相反，有人提出 p21 也可能作为癌基因发挥作用，因为它可以抑制细胞凋亡。因此，p21 被认为是一种具有双重行为的蛋白质，因为它的表达可能在乳腺癌中产生潜在的有益或危险的影响。因此，在针对乳腺癌患者进行 p21 表达靶向治疗时需要谨慎规划。这篇综述说明了 p21 的发现和诱导机制。然后，我们专注于阐明 p21 表达对人类乳腺癌发生的矛盾作用，并解释 p21 的亚细胞定位（核或细胞质）如何影响其作为细胞生长抑制剂或抗凋亡分子的命运，以及它对乳腺癌患者的临床病理因素和预后的影响。此外，我们探讨了 p21 的模式如何影响人类乳腺癌对化疗的反应性。还阐明了针对乳腺癌治疗靶向 p21 表达的药理学方法。
