Oncogenes, tumor suppressors, and apoptosis in cancer
The balance between cell proliferation and apoptosis is influenced by genes that contribute to the development of cancer (oncogenes) and those that encode proteins that normally suppress tumor formation (tumor suppressor genes).27 Oncogenes are mutated forms of normal cellular genes known as proto-oncogenes which, when activated by mutation or increased expression, increase the chance that a normal cell will become malignant.
In cancer cells, persistent and/or elevated signaling from oncogenes such as Myc, Ras, and E1A drive proliferation. In advanced malignancy, there is often selection for tumor cells with inactive p53 or over-expression of specific anti-apoptotic factors such as BCL2 — properties that enable the tumor cell to evade apoptosis. Increased BCL2 protein production occurs in numerous human cancers and is linked to poor disease outcome. In addition, over-expression of the BCL2 gene may confer resistance to chemotherapeutic drugs.28
As a consequence of such oncogenic lesions, tumor cells may in fact be innately more sensitive to the induction of apoptosis. For example, Myc is a powerful inducer of apoptosis under adverse conditions such as cellular stress, DNA damage, or when levels of survival factors are low.29,30 Myc may in fact enhance tumor cells' sensitivity to apoptotic signaling via death receptors, including DR4 and DR5.31,32 This duality may serve as an inbuilt check on the proliferative effects of Myc, and similar observations have been reported for almost all growth-promoting proteins.33