Reciprocal Rb inactivation and p16INK4 expression in primary lung cancers and cell lines.
cdk4-mediated phosphorylation of the retinoblastoma susceptibility protein (Rb) is stimulated by cyclin D1, an oncogene, and inhibited by p16, a candidate tumor suppressor. We examined these proteins in non-small cell lung cancer (NSCLC), which is predominantly Rb positive, and small cell lung cancer (SCLC), which is Rb negative. Most NSCLC and SCLC 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 in 18 of 27 NSCLC samples and abundant in 4 of 5 SCLC samples. Our data confirm the predicted reciprocity between Rb inactivation and p16 expression in a common human malignancy and define differential p16 expression as a fundamental distinction between NSCLC and SCLC.
Department of Medicine, Dana-Farber Cancer Institute, Boston, Massachusetts 02115.
G I
GI
Shapiro
C D
CD
Edwards
L
L
Kobzik
J
J
Godleski
W
W
Richards
D J
DJ
Sugarbaker
B J
BJ
Rollins
D015139:Blotting, Southern; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000032:analysis / Q000096:biosynthesis*; D002460:Cell Line; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004273:DNA, Neoplasm / Q000032:analysis; D015870:Gene Expression; D016161:Genes, Retinoblastoma; D016147:Genes, Tumor Suppressor; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D047428:Protein Kinase Inhibitors; D016160:Retinoblastoma Protein / Q000032:analysis / Q000096:biosynthesis; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004273:DNA, Neoplasm; D047428:Protein Kinase Inhibitors; D016160:Retinoblastoma Protein