Cell growth during
embryonic, fetal, and postnatal development, and in the normal maintenance of adult
tissues and organs requires the expression of genes that stimulate cells to divide at the
appropriate time and place. There are two classes of genes that are involved in the
regulation of normal cell growth: proto-oncogenes and tumor suppressor genes. These
genes got their names because of what happens when they are mutated, namely that tumors
form.
As shown in the upper part of the slide, normal cell growth and
proliferation is under the control of proto-oncogenes (which promote cell division) and
tumor suppressor genes (which suppress cell division). During normal cell growth and
proliferation, there needs to be a balance between the actions of these two classes of
genes. In cancer, there is an imbalance between the two. When proto-oncogenes
are mutated to oncogenes, they become "activated." That is, the oncogenes
either become constitutively active (they cannot be regulated), or they are overexpressed
(too much of an essentially normal product). When there is a loss (deletion) of
tumor suppressor genes, or when there are point mutations in tumor suppressor genes that
lead to a loss of function, the cell has lost the means to suppress the effects of
oncogenes. As shown in slide 2, human malignancy usually involves mutations of both
oncogenes and tumor suppressor genes.