INCREASED TELOMERASE ACTIVITY IN MOUSE SKIN PREMALIGNANT PROGRESSION

It has been postulated that the expression of the ribonucleoprotein te lomerase is necessary to overcome cellular senescence and that maligna nt tumors must express telomerase to maintain their immortality. In mo st human adult tissues, telomerase activity is not detected. In contra st, several murine tissues express various levels of telomerase. Mouse skin however, does not show telomerase activity. Using the mouse skin chemical carcinogenesis system, a well-characterized model for studyi ng premalignant and malignant progression, we assayed telomerase activ ity at various stages of premalignant papilloma progression by means o f the recently developed telomeric repeat amplification protocol. We o bserved that at 10 weeks of promotion, only one mouse skin papilloma o f 11 analyzed showed high levels of telomerase activity. The number of papillomas showing higher levels of telomerase activity increased at 20 weeks, and at 30 weeks of promotion, 100% of papillomas expressed s ignificantly higher levels of telomerase. We learned from previous stu dies that early papillomas are diploid, well-differentiated lesions, w hereas late papillomas are aneuploid and very dysplastic. It appears t hat the progressive increase in telomerase activity is associated with the increased level of genomic instability and the phenotypic progres sion of these premalignant tumors. It is also possible, however, that the increase in telomerase activity could be in part a consequence of an increase in the proportion of proliferating cells. Nevertheless, th e mouse skin system mag be a very useful in vivo model for the study a nd development of anti-telomerase therapeutic strategies.