![if !IE]> <![endif]>
Provirus and oncogenes are two key components that play very important role in the pathogenesis of tumors induced by viruses.
In provirus model, the gene enters the cell at the time of infection by tumor virus.
In oncogene model, the genes for malignancy are already present in all cells of the body by virtue of being present in the sperm and egg.
The oncogenic viruses have the ability to transform the cells in cultures and induce tumors in animals. The retroviruses may induce tumors by either of the two mechanisms: (a) by induc-ing or altering the expression of a preexisting cellular gene or (b) by introducing a new transforming gene (oncogene) into the cellular genome.
Oncogenes may be of two types: viral oncogenes and cellular oncogenes.
Viral oncogenes: Viral oncogenes are the genes that encodeproteins that induce transformation of normal cells into malig-nant cells. The viral oncogenes are usually of host cell origin. These oncogenes encode proteins that promote cell growth. The proteins encoded by oncogenes perform several functions. For example, the ras oncogene encodes a G protein that acts on the cell membrane, whereas myc oncogene encodes a tran-scription factor that acts on nucleus by binding to DNA. Viral oncogenes initiate inappropriate cell growth and malignant transformation, but are not required for the replication of viruses. Viral oncogenes of DNA and RNA viruses are summa-rized in Table 67-3.
Cellular oncogenes: Genes resembling viral oncogenes maybe of two types: cellular oncogenes and proto-oncogenes. The oncogenes isolated from cancer cells are known as cellular oncogenes (c-onc), while similar genes found in normal cells are called proto-oncogenes.
It is postulated that the cellular oncogenes may serve as precursor of viral oncogenes. Both cellular oncogenes and viral oncogenes are similar, but not identical. They differ from each other by their base sequences. Moreover, cellular onco-genes consist of introns characteristic of eukaryotic genes, but viral oncogenes do not contain any of these eukaryotic genes.
Transfection is the method of study of oncogenes, which canbe demonstrated in mouse fibroblast cell lines, such as NIH 3T3. Foreign DNA is taken up by these cells, incorporated into their genome, and is transfected into the host cells, resulting in the formation of transforming genes. These genes have been shown to be identical with that of cellular oncogenes.
Retroviruses (such as HTLV or HIV) carry a fourth gene, namely, tax or tat, next to the env gene. The tax or tat is a transactivatinggene that regulates the function of the viral genes. The onco-genic retroviruses may be slow transforming viruses or acute transforming viruses.
The slow transforming viruses, such as chronic leukemia viruses, have a low oncogenic potency and induce malignant changes, usually only of blood cells, and that after a long latent period. They replicate normally and do not transform cultured cells.
The acute transforming viruses, in contrast, are highly oncogenic. They induce malignancy in infected cells after a short latent period of weeks or months. They transform cells in culture and can cause different types of malignancies, such as sarcoma, carcinoma, and leukemia. Unlike slow transforming viruses, the acute transforming viruses are unable to replicate normally because they carry an additional gene, the viral oncogene (v-onc gene) on their genome, which replaces some of the genes necessary for replication of viruses. The v-onc gene can replicate only if coinfected with a standard helper retrovirus. Therefore, most of these acute transforming viruses are replica-tion defective viruses.
Rous sarcoma virus, however, is an exception, which is replication competent. It carries the oncogene src, which can replicate normally, because it consists of all the genomes gag, pol, and env, which are essential for normal replication.
Recombination between retroviral and cellular genes, gene amplification and mutations, chromosomal translocation, and promoter insertion are few of the genetic processes that appear to play important role in conversion of benign proto-oncogenes to cancer genes.
Copyright © 2018-2023 BrainKart.com; All Rights Reserved. Developed by Therithal info, Chennai.