The association of teromerase activity and teromere length with UV-carcinogenesis and photoaging of the skin

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We establoished the experimental protocol for the measurement of teromere fragment length (TRF) of epidermal and dermal DNA. Using 14 samples of normal skin, we could measure TRF in 11 eipdermal samples and 2 dermal samples. Epidemal TRF tends to shorten in association with the age. Epidermal samples from sun-exposed site and sun-protected site of two identifical persons were measured for TRF, showing slightlyk longer TRF of epidermis in sun-exposed skin than in sun-protected skin. Two cases of which the TRF of epidermis and dermis were compared showed the longer TRF and aging of the skin. To know whether ultraviolet light activates telomerase, we exposede HaCaT human keratinocytes to UVB (10, 20 and 30 mJ/cm^2) and telomerase activity was measured 48 hours later. The activity was strongest at the dose of 10 mJ/cm^2. The mechanisms are now under the investigation. The involvement of epidermal growth factor (EGF) signaling for telomerase activity in squamous cell carcinoma (SCC), a SCC cell line (HSC-1) being high in telomerase, was incubated with EGF-receptor blocker AG1478. This treatment induced the growth suppression and down-regulation of telomerase. AG1478 also suppressed the protein expression of myc and sp1 transcriptional factor, which usually up-regulate hTERT, an important subunit of telomerase. These result suggested that the inhibition of EGF signaling will lead to the control of the tumor growth of SCC in the skin.