Role of the p16 tumor suppressor gene in cancer.

摘要: Since its discovery as a CDKI (cyclin-dependent kinase inhibitor) in 1993, the tumor suppressor p16 (INK4A/MTS-1/CDKN2A) has gained widespread importance cancer. The frequent mutations and deletions of human cancer cell lines first suggested an important role for carcinogenesis. This genetic evidence causal was significantly strengthened by observation that frequently inactivated familial melanoma kindreds. then, high frequency gene alterations were observed many primary tumors. In neoplasms, is silenced at least three ways: homozygous deletion, methylation promoter, point mutation. two mechanisms comprise majority inactivation events most Additionally, loss may be early event progression, because deletion one copy quite some premalignant lesions. major target carcinogenesis, rivaled only p53 tumor-suppressor gene. Its mechanism action been elegantly elucidated involves binding to inactivating cyclin D-cyclin-dependent 4 (or 6) complex, thus renders retinoblastoma protein inactive. effect blocks transcription cell-cycle regulatory proteins results arrest. Although involved senescence, physiologic still unclear. Future work will focus on studies upstream lead expression regulation, perhaps better therapeutic strategies can improve clinical course lethal cancers.