Overexpression of cyclin D1 in mouse skin carcinogenesis.

Recent studies have provided evidence suggesting that disruption of cyclin function may play a critical role in tumorigenesis. Cyclin D1, a putative G1 cyclin previously isolated in human parathyroid adenomas (designated PRAD1) and mouse macrophages (designated Cyl1), has been implicated in various neoplasias including breast and squamous cell carcinomas (SCC). The role of cyclin altered regulation in the different stages of tumor progression has not been studied in a well defined animal model system. In the study presented here, Cyl1 was mapped to the distal end of mouse chromosome 7 and found to be dramatically overexpressed in skin SCC. In premalignant stages of tumor development, early papillomas showed basal Cyl1 transcript levels, whereas over-expression was observed in most advanced papillomas. These findings suggest that altered expression of cyclin D1 plays a critical role in mouse skin carcinogenesis and may be related to the acquisition of autonomous growth by papillomas. Further studies on the role of cyclin D1 in the mouse model system should prove valuable for understanding the multistep basis of tumor progression.