第9章 疾病与人类健康.ppt

Ras genes in human tumors have been shown to be activated by single point mutations predominantly involving codons 12, 13, 59 and 61. Approximately 50% of colorectal cancers and 95% of pancreatic cancers contain mutations of a RAS gene. A significant subset of acute nonlymphocytic leukemias, thyroid cancers and adenocarcinomas of the lung also contain such mutations. In most other tumor types (e.g. cancers of the breast, prostate, stomach, bladder, liver and brain), however Ras mutations do not occur often if at all. As RAS genes are ubiquitously expressed and presumably have similar functions in all cells, the basis for this tissue specificity is not understood. Activation of ras oncogenes by Chemical carcinogenes Cellular proto-oncogenes have been found in multiple copies in various tumors and transformed cell lines. The amplified proto-oncogene copies can occur in homogeneously staining chromosomal regions or double-minute chromosomes. The mechanism of gene amplification is not fully understood, illegitimate DNA replication occurring more than once during a single cell cycle could account for the increase of multiple segments (amplification units) of DNA from 200 to 2000 kb in size. All amplified proto-oncogenes express high levels of the corresponding RNA and protein and appear to be unrearranged. The amplified proto-oncogene is frequently tumor-specific; for example, N-myc or c-myc may be associated with the progression of neuroblastomas and small cell lung carcinoma cells. This suggests that increased expression of these proto-oncogenes plays a role in the development and progression of these tumors. The size of the HIV genome is similar to that of other retroviruses but it is more complex. There is no oncogene but there are extra open reading frames which do code for protein. In all 15 proteins are encoded in HIV and they are made because antibodies to them can be found in patients. These extra open reading frames are not typical of retroviruses such