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Overexpression of Cyclin D1 Enhances Gene Amplification¹

Department of Pharmacology [P. Z.], Columbia-Presbyterian Cancer Center [P. Z., W. J., I. B. W.] and Department of Genetics and Development [I. B. W.], Columbia University, New York, New York 10032, and Division of Environmental Health, School of Public Health, Ohio State University, Columbus, Ohio 43210-1240 [C. M. W.]

Defects in cell cycle control and increased genomic instability, including gene amplification, often occur during cancer development. Cyclin D1 plays a pivotal role in G₁, and this gene is frequently amplified and overexpressed in several types of human cancer. This study demonstrates that ectopic overexpression of cyclic D1 in a rat liver epithelial cell line markedly increased the yield of cells containing amplified copies of the CAD gene. This effect was associated with a loss of G₁-S checkpoint control, although the cyclin D1-overexpressing cells had a normal p53 gene. The capacity of cyclin D1 to enhance gene amplification may contribute to the process of genomic instability during tumor development.

¹ This study was supported by funding from the Markey Charitable Trust and the National Foundation for Cancer Research to I.B.W.

² Present address: The Salk Institute, La Jolla, CA 92037.

³ To whom requests for reprints should be addressed, at Columbia-Presbyterian Cancer Center, Room 1509, 701 West 168th Street, New York, NY 10032. Phone: (212) 305-6921; Fax: (212) 305-6889. E-mail: Weinstein@cuccfa.ccc.

Received 9/22/95. Accepted 11/13/95.

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