III. Oncogenes

B. DNA viruses

DNA viruses may become incorporated into the cell genome, but this step is not always necessary. Oncogenic DNA viral genes code for proteins that affect growth regulating substances in the cell.

1. Mechanisms of DNA oncogenesis include:

a. Interference with cellular inhibitors of growth, resulting in uncontrolled cell replication (e.g., the retinoblastoma gene product).

b. Activation of cellular DNA and RNA synthesis by viral protein products.

c. Insertional mutagenesis; viral DNA is inserted into the host genome and disrupts normal growth control.

d. Gene translocation and rearrangement.

2. DNA viruses shown to have an oncogenic role in human malignancies include:

a. Human papilloma virus (HPV) DNA sequences are found in over 80 percent of human uterine cervical cancer cells. HPV appears to be necessary but not sufficient for the development of most cervical cancers. See Chap. 36, sec. V.D.2 and Chap. 11, Cancer of the Uterine Cervix, sec. I.C.

b. Epstein-Barr virus (EBV) infects more than 90 percent of individuals in the first two decades of life, but generally causes no illness. EBV infects B lymphocytes and nasopharyngeal epithelium, both of which have a specific surface receptor for the virus. When EBV-infected cells are exposed to other proliferative stimuli, such as malaria, malignancy can result. EBV is a cofactor for the development of nasopharyngeal carcinoma in Asia, epidemic Burkitt‘s lymphoma, B-cell lymphomas in immunocompromised patients, cutaneous T-cell lymphoma (with HTLV-1), and gastric carcinoma. See Chap. 35, sec. IV.A.3.

c. Hepatitis B viral DNA sequences are found in the genomes of essentially all hepatocellular carcinomas. These sequences are translated into proteins that stimulate transcription. They also may cause cell transformation by insertional mutagenesis, which disrupts growth regulating genes.

d. Adenoviruses and polyoma viruses cause transformation of cells in cell culture but have not yet been shown to cause or contribute to human malignancy.

e. Human parvovirus oncosuppressive activity is discussed in Chap. 35, sec. IV.E.1.

Oncogenes are genes that cause malignant transformation of normal cells. They are consistently associated with malignancy and may be of either cellular or retroviral origin. In general, more than one oncogene is abnormally active in cancer. The multiple interactions among oncogenes that are necessary for cell division typically result in activation of many otherwise normal oncogenes. A one-to-one correspondence between most cancers and a single oncogene abnormality generally cannot be determined.

Дата добавления: 2015-06-04