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In this article we will discuss about causes for the oncogenicity of the oncogene.
When the oncogene from human bladder carcinoma cells was sequenced, and its sequence was compared with the sequence of the homologous proto-oncogene, its oncogenicity was found to result from a single base pair substitution.
That is, a single base pair difference was shown to correlate with the ability or inability of the two genes to transform “normal” cells growing in culture. The oncogene was apparently produced from its proto-oncogene by GC — TA trans version and this mutation results in the substitution of valine for the glycine present as 12th amino acid in the normal protein kinase.
At present, we do not know why such a small change in a proto-oncogene, a normal cellular gene, should produce an oncogene capable of producing transforming cells to the cancerous state. Recent studies have indicated that both the normal cells and the tumor cells of one patient with a bladder carcinoma may be heterozygous for the oncogene and the proto-oncogene.
This result suggests that the oncogene causes a predisposition, rather than an intermediate change, to the cancerous state. It has been postulated that chromosome breaks and rearrangements may have caused altered expression of proto-oncogenes or cellular oncogenes (Table 16.3).
Regardless of how oncogenes induce cancers, it now seems quite dear that retroviral oncogenes have evolved from normal cellular genes. Finally it can be concluded that the cancerous state is the end-product of multi-step process.
