OVEREXPRESSION OF CYCLIN-D1 IN MOUSE SKIN CARCINOGENESIS

Recent studies have provided evidence suggesting that disruption of cy clin 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 im plicated in various neoplasias including breast and squamous cell carc inomas (SCC). The role of cyclin altered regulation in the different s tages of tumor progression has not been studied in a well defined anim al model system. In the study presented here, Cyl1 was mapped to the d istal end of mouse chromosome 7 and found to be dramatically overexpre ssed in skin SCC. In premalignant stages of tumor development, early p apillomas showed basal Cyl1 transcript levels, whereas overexpression was observed in most advanced papillomas. These findings suggest that altered expression of cyclin D1 plays a critical role in mouse skin ca rcinogenesis and may be related to the acquisition of autonomous growt h by papillomas. Further studies on the role of cyclin D1 in the mouse model system should prove valuable for understanding the multistep ba sis of tumor progression.