DIFFERENTIAL-EXPRESSIONS OF CYCLIN-A AND THE RETINOBLASTOMA GENE-PRODUCT IN HISTOLOGICAL SUBTYPES OF LUNG-CANCER CELL-LINES

Cell-cycle-dependent phosphorylation of the tumor-suppressor protein p roduct of the retinoblastoma gene (RE) is mediated by a family of cycl in-dependent kinases and cyclins. We examined the expressions of RE pr otein and cyclin A protein in 13 small-cell lung cancer (SCLC) lines a nd 14 non-small-cell lung cancer (NSCLC) lines by immunoblotting. RE p rotein was not present or was of a mutant type in 77% of the SCLC line s (10/13) but was present in all the NSCLC lines. Cyclin A was express ed in 38% of the SCLC lines (5/13) and in 86% of the NSCLC lines (12/1 4). A positive correlation (P = 0.0034) between expression of cyclin A and wild-type RE protein was found by Fisher's exact probability test . Densitometric analysis of the expression of RE protein in RB(+) lung cancer lines showed that the phosphorylated form was predominant in 2 /3 of the SCLC and 8/14 of the NSCLC lines. The positive correlation b etween the expressions of RE protein and cyclin A suggests that RE pro tein in most RB(+) lung cancer cell lines is a target of cyclin-A-depe ndent kinase and that the tumor-suppressor function may be inactivated by phosphorylation.