Pande P, Mathur M, Shukla N K, Ralhan R
Department of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India.
Oral Oncol. 1998 Sep;34(5):396-403. doi: 10.1016/s1368-8375(98)00024-4.
Cyclin dependent kinase inhibitor 2/multiple tumour suppressor gene 1 (CDKN2/MTS1) and retinoblastoma (Rb) tumour suppressor genes play important roles in the regulation of the cell cycle. The protein products of these genes p16INK4 (p16) and pRb, respectively, like p53 protein inhibit progression from G1 to S phase. p16 exerts its function through inhibition of CDK4-mediated phosphorylation of pRb. The pRb/p16 pathway is a critical target for molecular aberration at the G1-S checkpoint in a wide range of primary human tumours. The expression of p16 and pRb proteins was analyzed by immunohistochemistry in 35 cases of oral squamous cell carcinomas (SCCs), 22 cases of premalignant oral lesions and 30 normal oral tissues. Lack of pRb expression was observed in 23/35 (66%) oral SCCs and 14/22 (64%) premalignant lesions. Lack of p16 expression was observed in 22/35 (63%) oral SCCs and 13/22 (59%) premalignant lesions. Weak p16 and pRb immunoreactivities were observed in normal oral mucosal epithelium. The status of p16 and pRb was correlated with clinicopathological characteristics of the patients. Alteration in p16 expression showed significant correlation with tumour staging and progression (P = 0.024). Alteration in pRb/p16 expression correlated with heavy consumption of betel and tobacco. Our results suggest that alterations in the p16/pRb pathway are early events in oral tumorigenesis and may be involved in the development of betel- and tobacco-related oral malignancies.
细胞周期蛋白依赖性激酶抑制剂2/多重肿瘤抑制基因1（CDKN2/MTS1）和视网膜母细胞瘤（Rb）肿瘤抑制基因在细胞周期调控中发挥重要作用。这些基因的蛋白质产物分别为p16INK4（p16）和pRb，与p53蛋白一样，可抑制细胞从G1期向S期进展。p16通过抑制CDK4介导的pRb磷酸化发挥其功能。在多种原发性人类肿瘤的G1-S检查点，pRb/p16通路是分子异常的关键靶点。采用免疫组织化学方法分析了35例口腔鳞状细胞癌（SCC）、22例口腔癌前病变和30例正常口腔组织中p16和pRb蛋白的表达情况。在23/35（66%）的口腔SCC和14/22（64%）的癌前病变中观察到pRb表达缺失。在22/35（63%）的口腔SCC和13/22（59%）的癌前病变中观察到p16表达缺失。在正常口腔黏膜上皮中观察到p16和pRb免疫反应较弱。p16和pRb的状态与患者的临床病理特征相关。p16表达改变与肿瘤分期和进展显著相关（P = 0.024）。pRb/p16表达改变与大量食用槟榔和烟草有关。我们的结果表明，p16/pRb通路的改变是口腔肿瘤发生的早期事件，可能参与槟榔和烟草相关口腔恶性肿瘤的发生发展。
