[医药卫生]癌基因与癌.ppt

癌基因与癌 Cancer causes about one-fifth of the deaths in the United States each year. Worldwide, between 100 and 350 of each 100,000 people die of cancer each year. Cancer is due to failures of the mechanisms that usually control the growth and proliferation of cells. During normal development and throughout adult life, intricate genetic control systems regulate the balance between cell birth and death in response to growth signals, growth-inhibiting signals, and death signals. A Multi-hit Model of Cancer Induction Is Supported by Several Lines of Evidence 第 一 节 癌 基 因Oncogenes A retrovirus may incorporate a cellular proto-oncogene during an infection. Subsequent mutation or other changes in the proto-oncogene make it oncogenic when the virus transfers it to a new cell in another infectious cycle. 二、细胞癌基因 细胞癌基因(cellular-oncogene, c-onc) 存在于生物正常细胞基因组中的癌基因，或称原癌基因 (proto-oncogenes , pro-onc) 。 第 二 节抑 癌 基 因Anti-oncogenes Retinoblastoma is caused by loss of both copies of the RB gene in chromosome band 13q14. In the inherited form, one chromosome has a deletion in this region, and the second copy is lost by somatic mutation in the individual. In the sporadic form, both copies are lost by individual somatic events. Retinoblastoma (RB) arises when both copies of the RB gene are deleted or inactivated. The RB product is a nuclear phosphoprotein whose state of phosphorylation controls entry into S phase. Nonphosphorylated RB sequesters隔离 the transcription factor E2F. The RB-E2F complex represses certain target genes. E2F is released when RB is phosphorylated by cyclin/cdk complexes; E2F can then activate genes whose products are needed for S phase. Loss of RB prevents repression by RB-E2F, and means that E2F is constitutively available. The cell cannot be restrained from proceeding through the cycle. Adenovirus E1A and papova virus T antigens bind to nonphosphorylated RB, and thus prevent it from binding to E2F. Loss of p53 alleles causes mice to die more rapid