PMID: 2488231Jan 1, 1989Paper

The molecular basis of cancer suppression by the retinoblastoma gene

Princess Takamatsu Symposia
W H Lee

Abstract

A class of cellular genes in which loss-of-function mutations are tumorigenic has been proposed. Such genes would normally act to suppress the cancer phenotype at the cellular or organism level. The gene determining susceptibility to hereditary retinoblastoma (RB) appears to operate in exactly this fashion, and is the first cancer suppressor gene to be molecularly cloned. The RB gene contains 27 exons dispersed over more than 200 kb and ubiquitously expresses a 4.7 kb mRNA. From sequence analysis of RB cDNA clones, the predicted RB protein has 928 amino acids. The RB protein is a nuclear phosphoprotein capable of binding to DNA and forming a complex with oncoproteins of several DNA tumor viruses. Consistent with its ubiquitous expression pattern, RB gene inactivation was found in many other cancers such as osteosarcoma, breast carcinoma, small cell lung carcinoma and prostate carcinoma. A cloned RB gene was introduced, via retrovirus-mediated gene transfer, into such tumor cells that have inactivated endogenous RB genes. Expression of the exogenous RB gene consistently suppressed their tumorigenicity in nude mice, suggesting that RB may act as a general cancer suppressor. In an attempt to address the potential cellular function...Continue Reading

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