Inactivation of tumor suppressor proteins in lung cancer.
It had been thought that the central molecular event in the malignant transformation of a cell is the mutation of certain oncogenes-and the resultant dysregulated activation of their encoded proteins. During the past decade, however, it has become clear that alteration of the activity of the protein products of tumor suppressor genes, through mutation or at the posttranslational level, is an equally basic and universal process in tumorigenesis. These proteins normally modulate cellular proliferation in the developing and adult organism, functioning as tumor suppressors by inhibiting inappropriate cell division. Therefore, inactivation of the normal function of tumor suppressor proteins removes important regulatory constraints on the cell, permitting the accelerated growth of cancerous tissue. The genesis of lung cancer is though to involve between 10 and 20 mutations. Of these, several are now known to involve tumor suppressor genes. In this review I will discuss the mechanism of tumor suppression by the protein encoded by one of these, the retinoblastoma gene, to illustrate precisely why the inactivation of tumor suppressors is a requisite step in cellular progression to lung and other carcinomas.
Weintraub
S J
SJ
Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, Saint Louis, Missouri 63110, USA.
D016147:Genes, Tumor Suppressor; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000503:physiopathology; D016160:Retinoblastoma Protein / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53