T. Fujishita et al., COINCIDENTAL ALTERATIONS OF P16(INK4A CDKN2) AND OTHER GENES IN HUMANLUNG-CANCER CELL-LINES/, Anticancer research, 18(3A), 1998, pp. 1537-1542
Cyclin-dependent kinase (CDK) inhibitor genes have recently been propo
sed as new tumor suppressor genes. To define the possible participatio
n of CDK inhibitor genes in lung carcinogenesis, we investigated the a
lterations of p15(INK4B), p16(INK4A), p21(Waf1), and p27(Kip1) genes i
n 34 human lung cancer cell lines using the polymerase chain reaction-
single strand conformation polymorphism (PCR-SSCP), direct sequencing,
and southern dot blot methods. Among the four CDK inhibitor genes, al
terations of only the p16(INK4A) gene were found in 8 out of 34 (24%)
cell lines, and all eight cell lines having a p16(INK4A) gene alterati
on had an alteration of either the K-ras or p53 gene. Conversely, p16(
INK4A) gene alterations were found in none of the 3 cell lines having
Rb gene alterations and none of the 3 cell lines having amplification
of the N-myc gene. Polymorphism was found in both p21(Waf1) and p27(Ki
p1) genes, but no association was found between the polymorphism and a
lterations of other genes. These results suggest that p16(INK4A) gene
alterations may play a certain role for lung carcinogenesis in co-oper
ation with either K- ras orp53 gene alterations.