Poyraz A, Akyürek N, Gönül I I, Erdem O
Dept. of Pathology, Gazi University Medical School, Ankara, Turkey.
J Exp Clin Cancer Res. 2004 Dec;23(4):625-31.
In response to DNA damage, p53 accumulates and regulates expression of several genes, including cyclin-dependent kinase inhibitor p21. Cells then undergo p21 dependent cell cycle arrest, which allows DNA damage repair and apoptosis. Bax is a death promoter member of the bcl-2 family which plays a central role in the regulation and commitment to programmed cell death. Breslow thickness is the most important factor in predicting prognosis for cutaneous malignant melanoma. In order to define the role of cyclin dependent kinase inhibitors and apoptosis regulators in invasion of malignant melanoma we investigated the expression of p21 and bax proteins. We observed that significant high p21 expression was associated with increasing Breslow thickness (Spearman correlation analysis, p=0.01). Additionally, Clark level I and II tumours expressed significantly lower p21 positivity than Clark level III, IV and V (p=0.006). Similarly, thick tumors showed a higher bax expression (p=0.012). Our results suggested that the role of p21 expression is more complicated in melanocytic skin cancers and abnormal regulation or abnormal function of cell cycle regulators occurred in the development and progression of malignant melanoma. In order to understand the role of bax expression in thick malignant melanomas and invasion biology, comparative analytic studies with other apoptosis regulators are needed.
为应对DNA损伤,p53会积累并调节多个基因的表达,包括细胞周期蛋白依赖性激酶抑制剂p21。然后细胞会经历p21依赖性细胞周期停滞,这使得DNA损伤得以修复并引发细胞凋亡。Bax是bcl-2家族的促死亡成员,在程序性细胞死亡的调控和进程中起核心作用。 Breslow厚度是预测皮肤恶性黑色素瘤预后的最重要因素。为了确定细胞周期蛋白依赖性激酶抑制剂和凋亡调节因子在恶性黑色素瘤侵袭中的作用,我们研究了p21和bax蛋白的表达。我们观察到,p21高表达与Breslow厚度增加相关(Spearman相关性分析,p = 0.01)。此外,Clark I级和II级肿瘤的p21阳性表达明显低于Clark III级、IV级和V级(p = 0.006)。同样,厚肿瘤显示出更高的bax表达(p = 0.012)。我们的结果表明,p21表达在黑素细胞性皮肤癌中的作用更为复杂,细胞周期调节因子的异常调节或功能异常发生在恶性黑色素瘤的发生和发展过程中。为了了解bax表达在厚恶性黑色素瘤和侵袭生物学中的作用,需要与其他凋亡调节因子进行比较分析研究。