ROLE OF THE RETINOBLASTOMA PROTEIN IN THE PATHOGENESIS OF HUMAN CANCER

The retinoblastoma gene (RE-I)was originally identified as the gene in volved in hereditary retinoblastoma. However, RB-I mutations are found in a number of common mesenchymal and epithelial malignancies. The re tinoblastoma protein (pRB) acts as a transcriptional regulator of gene s involved in DNA synthesis and cell-cycle control, In this regard, th e functional interaction between pRB and the E2F transcription factor family appears to be critical, The pRB-E2F interaction is, in turn, re gulated by a pathway that includes cyclin D1, cdk4, and p16. Mutations that affect this pathway have been documented in nearly every type of adult cancer, Thus, perturbation of pRB function may be required for the development of cancer, Insights into the biochemical functions of pRB, and its upstream regulators, may form the basis for the developme nt of novel antineoplastic agents. (C) 1997 by American Society of Cli nical Oncology.