The p53 tumor suppressor gene as a common cellular target in human carcinogenesis.
The p53 gene is a 16-20 kb of cellular DNA located on the short arm of human chromosome 17 at position 17p13.1. This gene encodes a 375-amino acid nuclear phosphoprotein which involves in the regulation of cell proliferation. The p53 gene was originally regarded as a dominant oncogene because its overexpression resulted in the immortalization of rodent cells, and the p53 gene could transform rat embryonic fibroblasts in concert with an activated ras gene. It soon became clear, however, that many of the p53 clones that had been studied were in fact mutated versions of the gene, and the wild-type p53 actually acts as a tumor suppressor. Loss of normal p53 function has been associated with the cell transformation in vitro and the development of neoplasms in vivo. More than one-half of human malignancies derived from the epithelial, mesenchymal, hematopoietic, and lymphoid tissues, as well as the central nervous system, analyzed thus far, were shown to contain an altered p53 gene. Most p53 gene alterations are the missense mutations, giving rise to an altered protein. These mutations are most frequently located in the evolutionally conserved areas. Furthermore, it has been demonstrated that the SV40 large T antigen, the adenovirus E1B protein, and papillomavirus E6 protein can bind to wild-type p53 protein and presumably lead to inactivation of this gene product as well. Therefore, the inactivation of normal (or wild-type) p53 is currently regarded as an important genetic pathway for human carcinogenesis generated by endogenous factors and exogenous carcinogens, as well as several tumor viruses. The current data on the p53 gene and its alterations in human malignancies, particularly those in the gastrointestinal tract, are reviewed.
Chang
F
F
Department of Pathology, Kuopio Cancer Research Centre, University of Kuopio, Finland.
Syrjänen
S
S
Kurvinen
K
K
Syrjänen
K
K
D000595:Amino Acid Sequence; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D005770:Gastrointestinal Neoplasms / Q000235:genetics; D016158:Genes, p53 / Q000235:genetics / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D016159:Tumor Suppressor Protein p53