1.
Specific Aims : Telomerase is a ribonucleoprotein enzyme responsible for maintaining the length of the telomere (end region) of chromosomal DNA (1,4-7,18). Telomerase activity (TA) is present in germinal tissues and fetal tissue but is not detectable shortly after birth in almost all somatic cells (16,21,23,33). Shortening of telomeres occurs with successive cell divisions in somatic cells, in the absence of telomerase activity (13,17,24,28). In human neoplastic cells, but not surrounding normal tissues, telomerase activity is found to be markedly elevated 13,10- 16,26). Therefore, it has been hypothesized that tumor cells become immortalized because chromosomal stability is imparted by telomerase (2,26). We have shown that TA is elevated in skin tumors of the head and neck (unpublished observations). Moreover, the surrounding nonmalignant (sundamaged) skin also possess TA, albeit at lower levels. The presence of TA in surrounding nontumor tissue contrasts with the complete absence of TA in skin samples from sun-protected buttock skin. This finding of TA in both tumors an tumor-susceptible skin provides an extraordinary model to study mechanisms by which telomerase reactivation influences malignant progression. Here we propose to study TA in skin.
Specific aims are;
Aim #1 : To determine if skin tumor cells are responsible for expressing TA.
Aim #2 : To determine if tumor infiltrating lymphocytes express TA.
Aim #3 : To determine if """"""""stem"""""""" cells in peritumoral skin express TA.
Aim #4; To determine if ultraviolet radiation plays a role in upregulation of TA in peritumoral skin.
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