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Reciprocal Rb Inactivation and p16^INK4 Expression in Primary Lung Cancers and Cell Lines¹

Department of Medicine, Dana-Farber Cancer Institute [G. I. S., C. D. E., B. J. R.], and Department of Pathology [L. K., J. G.] and Division of Thoracic Surgery [W. R., D. J. S.], Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115

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.

¹ Supported by Grants CA19589 to B. J. R and CA59594 to D. J. S from the NIH, by a Women's Cancers Program Fellowship Grant from the Dana-Farber Cancer Institute to G. I. S., and by an American Cancer Society Junior Faculty Research Award to B. J. R.

² To whom requests for reprints should be addressed, at D930, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115.

Received 11/ 4/94. Accepted 12/19/94.

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