DEREGULATED EXPRESSION OF CYCLIN D1 AND OTHER CELL CYCLE-RELATED GENES IN CARCINOGEN-INDUCED RAT MAMMARY-TUMORS

Dysregulation of cyclin expression has been reported for several human malignancies, including breast cancer. To further investigate the rol e of cyclin genes in mammary tumorigenesis we analyzed the expression of cyclins D1, E and A and other cell cycle-related proteins in a seri es of nine N-methyl-N-nitrosourea-induced primary rat mammary tumors, Western blot analysis revealed a 10- to 15-fold increase in the level of cyclin D1 protein in most (7/9) of the tumors, when compared with n ormal rat mammary gland, The two tumors that did not show this increas e also displayed negligible levels of the retinoblastoma protein, A mo derate increase, 1.5- to 2-fold, in the level of cyclin E was observed in four tumors and three tumors displayed abnormal low molecular weig ht cyclin E-related proteins, None of the tumors showed amplification of the cyclin D1 or E genes when studied by Southern blot analysis, Al l nine tumors showed a 2- to 6-fold increase in the level of cyclin A protein, Most of the tumors also displayed a marked increase in levels of the CDK2 and CDK4 proteins, These changes did not appear to be sim ply a consequence of increased cell proliferation, as assessed by prol iferating cell nuclear antigen analysis, Thus, aberrant expression of cyclins and other cyclin-related genes occurs frequently in mammary tu morigenesis in both rodents and humans.