CYCLIN D AND CYCLIN DEPENDENT KINASE INHIBITORS

细胞周期控制需要对G1检查点的调节 和基因组的不稳定性。细胞周期蛋白D1经常过度表达 在人类癌症中被放大。我们已经证明，人类的过度表达 细胞周期蛋白D1下调转化生长因子-β的表达 并降低转化生长因子-β1的生长抑制作用 在永生化的人食道上皮细胞系中。这个 细胞周期蛋白依赖性激酶抑制物，如p15、p16、p18和p19是 可能的肿瘤抑制基因。P15和p16基因突变失活 是肺癌肿瘤进展的晚期事件。P16可以抑制 人癌细胞系的生长和致瘤性。基因突变 P18和p19在人类癌症中很少见。

The regulation of the G1 checkpoint is required for cell cycle control and genomic instability. Cyclin D1 is frequently overexpressed and amplified in human cancers. We have shown that overexpression of human cyclin D1 downregulates the transforming growth factor beta (TGF-beta) type II receptor and reduces the growth inhibitory effects of TGF-beta1 in an immortalized human esophageal epithelial cell line. The cyclin-dependent kinase inhibitors, e.g., p15, p16, p18 and p19, are putative tumor suppressor genes. Mutational inactivation of p15 and p16 are late events in tumor progression of lung cancer. p16 can suppress growth and tumorigenicity of human carcinoma cell lines. Mutations in p18 and p19 are rare in human cancers.