The role of ‘tumor suppressor’ genes in neural tumors

Abstract

very cell contains the genetic capacity for rapid growth dur- ing embryonic development, as well as the ability to differentiate and assume its function in the tissue structure. Clearly, an over- lapping set of genes in different cell types must be involved in these processes and in the response of cells to their environment. In ad- dition to genes that stimulate growth and differentiation (e.g. certain proto-oncogenes), most (if not all) cells seem to contain 'tumor suppressor' genes against excessive growth. The function of these 'tumor suppressor' genes may be to regulate (suppress) the expression of growth-promoting factors, thereby exercising growth control. There are different types of genetic alterations capable of in- itiating tumor development, includ- ing loss or altered expression of endogenous tumor suppressor genes and/or invasion of virus genes that could lead to loss of growth regulation. Depending on the nature of these initial and subsequent genetic changes, un- inhibited growth of the cells could progress to benign or malignant tumor formation. Several research strategies have led to the dis- covery of genes involved in tumor formation in the nervous system in both positive and negative ways. This article focuses on the 'tumor suppressor' genes - who they are, what they do, how they are inacti- vated, and how to identify new can- didates (for a review of positively active oncogenes, see Ref. 1). Who they are Several avenues of research have provided evidence for the existence of tumor suppressor genes. For example, fusion of normal and malignant cells leads to the suppression of the tumorigenic phenotype in most of the resulting hybrids, which retain a relatively complete chromosomal com- plement. Reappearance of tumori- genicity is often accompanied by