Physical associations between cyclins, viral oncogenes and tumour suppressor genes imply a central role for cyclins in growth control 1, 2. Cyclin D1 was identified as a candidate oncogene (PRAD1) in tumour-specific DNA rearrangements3, 4. and is suspected to be a contributor to several types of neoplasms including breast cancer 5, 6. Cyclin D1 also rescues G1 cyclin-defective Saccharomyces cerevisiae 7, and is a growth-regulated gene8. Despite evidence suggesting that cyclin D1 is an oncogene, its ability to transform cells directly in culture remains controversial9-16. To evaluate its potential to deregulate growth in vivo in a physiologically relevant tissue we overexpressed cyclin Dl in mammary cells in transgenic mice. We report here that overexpression of cyclin Dl resulted in abnormal mammary cell proliferation including the development of mammary adenocarcinomas. We conclude that overexpression of cyclin Dl deregulates cell proliferation and can induce tumorigenic changes in mammary tissues, suggesting that cyclin Dl indeed plays an important oncogenic role in breast cancer.
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