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 thought 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.