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

建立了测定表皮和真皮DNA端粒片段长度（TRF）的实验方案。使用14个正常皮肤样本，我们可以测量11个表皮样本和2个真皮样本的TRF。表皮TRF随年龄的增长而缩短。对同一个人的日晒部位和防晒部位的表皮样品进行了TRF测量，结果显示，日晒部位的表皮TRF略长于防晒部位。比较表皮和真皮层的TRF，两例患者的TRF变长，皮肤老化。为了了解紫外光是否激活端粒酶，我们将HaCaT人角质形成细胞暴露在UVB（10、20和30 mJ/cm^2）下，并在48小时后测量端粒酶活性。在10 mJ/cm^2剂量下活性最强。目前正在对这些机制进行调查。用EGF受体阻滞剂AG1478培养了端粒酶含量高的鳞状细胞癌（SCC）细胞系（HSC-1）中表皮生长因子（EGF）信号通路参与端粒酶活性的研究。该处理诱导了端粒酶的生长抑制和下调。AG1478还抑制了myc和sp1转录因子的蛋白表达，这些转录因子通常上调端粒酶重要亚基hTERT。这些结果提示，抑制EGF信号传导将导致皮肤SCC肿瘤生长的控制。

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.