Angiogenesis: A mechanism by which oncogenes and tumor suppressor genes regulate tumorigenesis

Abstract

Normal cells become malignant in a tissue culture flask, in experimental animals, and in cancer patients, largely as a result of the accumulation of a series of genetic lesions that activate proto-oncogenes to oncogenes and that inactivate tumor suppressor genes, sometimes called anti-oncogenes [1]. About 50 oncogenes and a dozen anti-oncogenes have been cloned and sequenced. The functions of most of them are well understood in the sense that the primary structure and biochemical activity of the proteins they encode are known. The vast majority of these proteins are either transcription factors or participants in signal transduction pathways (see Chapter 1). However, the identification of an oncogene-encoded protein as a transcription factor or a member of a signal transduction pathway does not fully explain why an increase in its activity (or its loss of function in the case of the anti-oncogenic tumor suppressor genes) increases the likelihood that a cell will become tumorigenic. A complete understanding of how the activation of an oncogene contributes to tumorigenicity demands additional information. It requires (1) that the oncogene-regulated genes be identified and the function of their protein products determined and (2) that those oncogene-regulated proteins that play a crucial role in the development of the tumorigenic phenotype be differentiated from those that are irrelevant. One way to begin to identify crucial oncogene- and tumor suppressor generegulated proteins is to investigate molecules that control a phenotype known to be essential for tumor growth and then to determine if the production of such proteins is altered by oncogene activation or by suppressor gene loss. One phenotype that is particularly amenable to such analysis is angiogenesis — the ability to induce neovascularization or new blood vessel growth.