Transcription factors and cancer: an overview

Cancer represents the out-of-control proliferation of a particular cell type, which originates with an unwanted mutation, followed by an accumulation of defects in many classes of genes. The two well-known types of primary genes that govern cell division and are responsible for cancer include: protooncogenes (gain-of-function) that serve as accelerators to activate the cell cycle, and tumor suppressor genes (loss-of-function) that serve as brakes to slow the growth of cells. There are now 17 known signal transduction pathways, plus at least two stress-response pathways; all of these appear to be highly conserved in nematodes, flies and all vertebrates. Ultimately, transcription factors participate at the ends of all 19 pathways-by causing the up- or down-regulation of specific genes. All primary and modifier genes leading to cancer participate in one or another of these pathways. Innumerable exogenous and (autocrine and paracrine) endogenous signals bombard our cells each day and all are channeled through these 19 pathways, leading to the cell's response to these signals. Tumor progression represents a loss of normal cross-talk between cells, breakdown in communication between classes of genes, DNA methylation abnormalities, genetic instability, and hypermutability. Cancer is thus a multiplex phenotype: a crescendo of defects in hundreds if not thousands of genes, as a function of time, leading to an invasive and lethal disease. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.