Obiettivo
CANCER IS A DISEASE CHARACTERIZED BY LOSS OF CELLULAR GROWTH CONTROL. AS SUCH, IT IS NOT SURPRISING THAT THE MOLECULAR MACHINERY OF THE CELL CYCLE IS INVOLVED IN TUMORIGENESIS. RECENT DISCOVERIES HAVE BROUGHT SEVERAL CELL-CYCLE REGULATORS INTO SHARP FOCUS AS FACTORS IN HUMAN CANCER. AMONG THE MOST CONSPICUOUS TYPES OF MOLECULE TO EMERGE FROM ONGOING STUDIES IN THIS FIELD ARE THE CYCLIN-DEPENDENT KINASE INHIBITORS SUCH AS p15 AND p16. THE EMPLOYMENT OF SUITABLE ANIMAL MODEL SYSTEMS WOULD GREATLY FACILITATE THE INVESTIGATION OF THESE GENES IN THE PRESENT PROJECT IT IS INTENDED TO USE THE MULTISTAGE SKIN CARCINOGENESIS MODEL BECAUSE THE STAGES OF INITIATION, PROMOTION AND PROGRESSION ARE WELL CHARACTERIZED. THE AIM IS TO ADOPT TWO COMPLEMENTARY APPROACHES. THE FIRST IS DESIGNED TO ANALYSE IN DETAIL THE GENETIC ALTERATIONS OF p15 AND p16 GENES. THIS ANALYSIS GIVES US THE OPPORTUNITY TO IDENTIFY THESE GENES AS TARGETS FOR THE ACTION OF CARCINOGENS.
THE SECOND IS BASED ON THE IDENTIFICATION OF FUNCTIONAL ALTERATIONS OF THESE GENES ASSOCIATED WITH SPECIFIC STAGES OF CARCINOGENESIS.
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