RECIPROCAL RB INACTIVATION AND P16(INK4) EXPRESSION IN PRIMARY LUNG CANCERS AND CELL-LINES

cdk4-mediated phosphorylation of the retinoblastoma susceptibility pro tein (Rb) is stimulated by cyclin D1, an oncogene, and inhibited hg p1 6, a candidate tumor suppressor. We examined these proteins in non-sma ll cell lung cancer (NSCLC), which is predominantly Rb positive, and s mall cell lung cancer (SCLC), which is Rh negative. Most NSCLC and SCL C resection specimens and cell lines overexpress cyclin D1 (indicating that cyclin D1 overexpression and Rb inactivation can coexist in SCLC ). However, 9 of 9 Rb-positive NSCLC cell lines have absent or low p16 , while an Rb-negative NSCLC line and 5 of 5 SCLC cell lines have high levels of p16. In primary resection specimens, p16 was undetectable i n 18 of 27 NSCLC samples and abundant in 4 of 5 SCLC samples. Our data confirm the predicted reciprocity between Rh inactivation and p16 exp ression in a common human malignancy and define differential p16 expre ssion as a fundamental distinction between NSCLC and SCLC.