Genes that confer the ability to convert cells to a tumourigenic state are called oncogenes. Cancer cells are characterised by immortalization, transformation and metastasis. Oncogenes induce uncontrolled cell growth resulting in tumour, so it can be anticipated that the products of these genes would act by stimulating cell division in some manner.
Now it is clear that the products of these oncogenes play various roles in regulating cell division in one or more cell types.
The oncogene products may be similar to growth-factor or hormone-receptor, or may be the analogue of nuclear receptor. They may encode for protein kinase that phosphorylate tyrosine residues. Some of them encode nuclear transcription factors which activate the expression of specific genes whose products function as positive regulators of cell division.
There are two classes of oncogenes — one is viral oncogene present in viruses that causes the transformation of target cells. The counterpart of which stays within the host cell involved in normal cellular functions are called cellular oncogenes. The cellular sequences themselves are not oncogenic, are described as proto-oncogenes, whose capture by retrovirus and subsequent modification may create an oncogene.
Oncogenic potential of tumour virus resides in a single function or a group of related functions that are active early in the viral lytic cycle. Tumour viruses carry genes (v-one) which confer on them the ability to convert host cell into tumourigenic state. About 100 viral oncogenes have been identified so far.
When transformation occurs, the relevant genes are integrated into the genomes of transformed cells and expressed constitutively. Oncogenes of DNA tumour viruses do not have cellular counterparts. In case of non- defective RNA viruses, tumourigenicity does not rely upon an individual viral oncogene, but upon the ability of the virus to activate a cellular proto- oncogene.
Acute transforming retroviruses capture cellular oncogene (absent in ancestral virus) by means of a transduction event during an infective cycle. At least 25 c-onc genes have been identified by their representation in retroviruses. Viral infection is not really necessary for tumour formation as evidenced by transfection assay.
Proto-oncogenes may also be activated by insertion, translocations or amplification of DNA sequences although nucleotide sequence remains unaltered (c-myc). Proto-oncogenes can be activated by mutation (c-ras). Activation of ‘tumour suppressor genes’ may also be responsible for unconstrained growth of cancer cells.
When we compare a viral oncogene (v-onc) sequence with a corresponding cellular oncogene (c-onc) sequence, we find that the organization of the viral gene corresponds to the mRNA of the c-onc gene, but the v-onc genes consist of uninterrupted coding sequences, while the c-onc genes have the usual genomic organisation of alternating exon and intron.
The cellular oncogenes and proto-oncogenes have multiple exons separated by introns, whereas the viral oncogenes are single exons. For example, chicken cellular src proto-oncogene contains 11 introns separating 12 coding sequences, whereas the RSV v-src gene has a single, uninterrupted coding sequence.
Both the genes code for protein kinases that phosphorylate tyrosine residues, ^both the protein can interact with same antibody. It has been found that there are 18 single nucleotide pair differences between the coding sequences of v-src and c-src that result in 8 amino acid changes in the protein products, but those must not be involved in oncogenecity.
In several cases, the v-onc coding sequence appears to have evolved only relatively little from the c-onc sequence, usually by point mutations.
An indication that the v-onc genes retain functions related to their c-onc progenitors, is provided by the fact that the majority of nucleotide changes are located in third base positions where they do not affect the protein sequence. So, in a word, viral oncogenes and cellular oncogenes are almost same, but the cellular oncogenes are present as proto-oncogene.
These proto-oncogenes can mutate to form that are capable of inducing oncogenesis.