Genes that suppress tumors: What turns them off?

Tumor suppressor genes, as their name implies, work as negative effectors of cell growth, inhibiting cell division. There are presumed to be many tumor suppressor genes in the genome, and each has its own role in preventing the rampant behavior of cancer cells. Therefore, there are numerous potential targets of ionizing radiation (IR) that can lead to interruption of normal behavior. Tumor suppressor genes often appear to be a target for the relatively random damaging nature of IR because their function needs only to be abrogated for a cell to move one step closer to malignancy. Damage more or less anywhere on (a) broadly defined region(s) of the gene can result in this loss of function. Of course, the extent of dysfunction will depend on the gene and on the cell because the degree of utilization of each gene is often dependent on the tissue origin of the cell. So, damage of any one gene may have a greater impact on one type of cell than on another.

In this way, tumor suppressor genes are unlike the proto-oncogenes that require specific mutations to become oncogenes, which can then potentially transform premalignant cells into malignant cells. Whereas the proto-oncogene may be considered the signal that turns the cells “on,” the tumor suppressor gene serves as the “off” signal.

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