Am. J. Respir. Cell Mol. Biol., Vol 15, No. 2, Aug 1996, 150-155.
Inactivation of tumor suppressor proteins in lung cancer
SJ Weintraub
Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, Saint Louis, Missouri 63110, USA.
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.
