TUMORIGENICITY AND GENE AMPLIFICATION POTENTIALS OF CYCLIN D1-OVEREXPRESSING NIH3T3 CELLS

Cyclin D1 is a key regulator of the G1-S transition in cell cycle, and its gene is amplified and overexpressed in many cancers. To address t he gene amplification potential of the cells in which the cyclin D1 ge ne expression is deregulated, we have established NIH3T3 clones with v arious levels of cyclin D1 transgene message. Those transfectants show ed anchorage independent growth and tumorigenicity without in vitro mo rphological transformation. The degree of the transformed phenotype ap parently correlated with the cyclin D1 expression level. Upon selectio n by N-(phosphonoacetyl)-L-aspartate (PALA), the cyclin D1-transfected NIH3T3 cells showed a higher ability to develop PALA-resistant coloni es by amplifying the CAD gene, as compared to the parental NIH3T3 cell s. (C) 1995 Academic Press, Inc.