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

端粒酶活性和端粒长度与皮肤紫外线致癌和光老化的关系

• 批准号: 12670820
• 负责人: UEDA Masato
• 金额: $ 0.77万
• 依托单位: Kobe University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670820/
• 关键词: skin; telomere; telomerase; aging; UV; EGF; transcription factor; hTERT; テロメラ-ゼ; 表皮細胞; 細胞増殖

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.

建立了表皮和真皮DNA端粒片段长度（TRF）测定的实验方法。用14例正常皮肤标本，11例表皮标本和2例真皮标本可测得TRF。表皮TRF有随年龄增长而缩短的趋势。对两个相同个体的暴露部位和防晒部位的表皮样品进行了TRF测定，发现暴露皮肤的TRF略长于防晒皮肤。其中2例比较了表皮和真皮的TRF，显示皮肤的TRF较长，皮肤老化。为了了解紫外线是否激活端粒酶，我们将HaCaT人角质形成细胞暴露于UVB（10、20和30 mJ/cm ^2），48小时后测量端粒酶活性。剂量为10 mJ/cm ^2时活性最强。目前正在调查这些机制。表皮生长因子（EGF）受体阻断剂AG 1478与鳞状细胞癌（SCC）细胞系（HSC-1）中端粒酶活性的参与表皮生长因子（EGF）信号转导。此处理诱导生长抑制和端粒酶下调。AG 1478还抑制myc和sp1转录因子的蛋白表达，这两种转录因子通常上调端粒酶的重要亚基hTERT。这些结果表明，EGF信号的抑制将导致控制皮肤SCC的肿瘤生长。

项目成果

Ahmed NU, et al.: "Aberrant expression of MSO1 transcriptional activator in human in vivo"Pigment Cell Res. 14. 140-143 (2001)

Ahmed NU 等人：“人体内 MSO1 转录激活因子的异常表达”Pigment Cell Res。

Ichihashi M, Ueda M, Budiyanto A, Araki K, Funasaka Y: "Sunlight and skin cancer"Environment Sci. 7. 203-227 (2000)

Ichihashi M、Ueda M、Budiyanto A、Araki K、Funasaka Y：“阳光与皮肤癌”环境科学。

budiningsih S, Prihartono J, Ohno Y, Hamzah M, Ichihashi M, Cornain S, Ueda M, Kanoko M, Mukhtar A, Tjarta A, Poetiray E, Munakata N, Cipto H: "Epidemiological characteristics of non-melanoma skin cancer in Indonesia : preliminary results"Med J Indones. 9

budiningsih S、Prihartono J、Ohno Y、Hamzah M、Ichihashi M、Cornain S、Ueda M、Kanoko M、Mukhtar A、Tjarta A、Poetiray E、Munakata N、Cipto H：“印度尼西亚非黑色素瘤皮肤癌的流行病学特征

Ueda M, Kanoko M, Cornain S, Hamzah M, Poetiray E, Prihartono J, Ohno Y, Ichihashi M: "Molecular pathological changes induced by ultraviolet light during the development of skin cancer"Med J Indones. 9. 118-122 (2000)

Ueda M、Kanoko M、Cornain S、Hamzah M、Poetiray E、Prihartono J、Ohno Y、Ichihashi M：“皮肤癌发生过程中紫外线诱导的分子病理变化”Med J Indones。

Tsukamoto K, Ueda M, Hirata S, Osada A, Kitamura R, Takashima T, Ichihashi M, Shimada S: "gp100 mRNA is more sensitive than tyrosinase mRNA for RT-PCR amplifiation to detect circulating melanoma cells in peripheral blood of melanoma patients"J Dermatol Sc

Tsukamoto K、Ueda M、Hirata S、Osada A、Kitamura R、Takashima T、Ichihashi M、Shimada S：“在 RT-PCR 扩增中，gp100 mRNA 比酪氨酸酶 mRNA 更敏感，可检测黑色素瘤患者外周血中的循环黑色素瘤细胞”