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.