Cell cycle dependent phosphorylation of the RB tumor suppressor protein is mediated by a family of G1 cyclin dependent kinases (cdks) and cyclins including the activated cdk4:cyclin D complex. The identification of a cdk4 inhibitor, p16(INK4), as a target for mutations in cultured tumor lines and primary tumors suggested that RB activity may be affected in these cells. We have examined 88 lung cancer lines for p16(INK4) protein expression and have observed a striking inverse correlation between the presence of p16(INK4) and wildtype RB. We demonstrated that only 6/55 (11%) of small cell lung cancer (SCLC) samples had absent p16(INK4) protein, and all 6 belonged to the rare subset of SCLC with wildtype RB expression. Conversely of 48 SCLC samples with absent or mutant RB, all showed detectable levels of p16(INK4) protein. In contrast, we observed that 23/33 (70%) of non-SCLC samples had loss of p16(INK4). Twenty-two of 26 non-SCLC lines with wildtype RB had absent p16(INK4) while 6 of 7 non-SCLC lines with absent or mutant RB had detectable p16(INK4). The inverse correlation of RB and p16(INK4) expression and the absence of p16(INK4) inactivation in RB (-/-) SCLC lines (0/48) confirms a common p16(INK4)/RB growth suppressor pathway in human cancers and provides evidence that p16(INK4), and not an adjacent gene on chromosome 9p, is a specific target for mutational events.
|Original language||English (US)|
|Number of pages||4|
|State||Published - Jan 1 1994|