Mechanisms of UVA-induced skin cancer
UVA 诱发皮肤癌的机制
基本信息
- 批准号:8651484
- 负责人:
- 金额:$ 36.49万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2010
- 资助国家:美国
- 起止时间:2010-08-09 至 2016-03-31
- 项目状态:已结题
- 来源:
- 关键词:ApoptosisBiochemicalBiologicalCell physiologyChromosomes, Human, Pair 10DNA DamageDNA RepairDNA damage checkpointDataDevelopmentDiseaseDominant-Negative MutationDown-RegulationEP300 geneEnvironmental Risk FactorEpidermisGenetic TranscriptionGoalsHomologous GeneHumanKnowledgeMalignant NeoplasmsMediatingMolecularMusPTEN genePathogenesisPathway interactionsPhosphoric Monoester HydrolasesPredispositionPreventionPreventiveResearchRoleSchemeSkinSkin CancerSkin CarcinogenesisSkin CarcinomaSmall Interfering RNASunlightTestingTherapeuticTumor Suppressor ProteinsTumorigenicityUltraviolet A radiationUltraviolet B RadiationUltraviolet Raysbaseburden of illnesscancer riskenhancing factorgene environment interactionimprovedin vivoinsightirradiationkeratinocyteknock-downoverexpressionpreventpublic health relevancerepairedresearch studyresponsesoundtensintumorigenesisultravioletultraviolet irradiation
项目摘要
DESCRIPTION (provided by applicant): The long-term goal of this research is to determine the molecular/cellular basis for the gene- environment interactions in the pathogenesis of skin cancer. The major environmental risk factor for non-melanoma skin cancer is ultraviolet (UV) radiation in sunlight including UVB and UVA. Although UVA has different physical and biological targets from UVB, the UVA contribution to skin cancer susceptibility and its molecular basis is unclear. Preliminary data within this proposal demonstrate that a critical suppressor for human and mouse skin cancer is PTEN (phosphatase and tensin homologue deleted on chromosome 10). In epidermal keratinocytes, PTEN transcription is significantly down-regulated by UVA, whereas targeted deletion of PTEN in the epidermis accelerates skin carcinogenesis. Although the precise mechanisms responsible for the enhanced susceptibility to skin tumorigenesis are unknown, preliminary data within this proposal show that PTEN loss may impair repair and checkpoints in response to DNA damage. The central hypothesis of the proposed experiments is that UVA-induced down-regulation of PTEN transcription inhibits DNA repair and DNA damage checkpoints and thus increases skin cancer susceptibility. The overall aim of this proposal is to determine the molecular mechanisms and consequences of UVA-induced PTEN down-regulation. The specific aims are to (1) test the hypothesis that PTEN down-regulation inhibits DNA repair and DNA damage checkpoints in response to low-level UV irradiation; (2) elucidate upstream regulators critical for UVA-induced down-regulation of PTEN transcription; and (3) analyze the consequences of PTEN down- regulation in skin cancer susceptibility in vivo. These experiments will provide new insights into the molecular and cellular basis for the UVA contribution to skin carcinogenesis. This knowledge can be used to develop better strategies to prevent and treat skin cancer.
描述(申请人提供):这项研究的长期目标是确定皮肤癌发病机制中基因-环境相互作用的分子/细胞基础。非黑色素瘤皮肤癌的主要环境风险因素是阳光下的紫外线(UV)辐射,包括UVB和UVA。尽管UVA与UVB具有不同的物理和生物靶点,但UVA对皮肤癌易感性的贡献及其分子基础尚不清楚。这项建议中的初步数据表明,人类和小鼠皮肤癌的关键抑制因子是PTEN(10号染色体上缺失的磷酸酶和张力蛋白同源物)。在表皮角质形成细胞中,PTEN转录被UVA显著下调,而在表皮中PTEN的靶向缺失则加速了皮肤癌的发生。尽管导致皮肤肿瘤易感性增加的确切机制尚不清楚,但该方案中的初步数据显示,PTEN缺失可能会损害对DNA损伤的修复和检查点。拟议实验的中心假设是,UVA诱导PTEN转录下调会抑制DNA修复和DNA损伤检查点,从而增加皮肤癌的易感性。这项建议的总体目标是确定UVA诱导PTEN下调的分子机制和后果。其具体目的是(1)验证PTEN下调抑制DNA修复和DNA损伤检查点的假说;(2)阐明对UVA诱导PTEN转录下调至关重要的上游调控因子;(3)分析PTEN下调在体内皮肤癌易感性中的后果。这些实验将为长波紫外线在皮肤癌发生中的分子和细胞基础提供新的见解。这些知识可以用来开发更好的策略来预防和治疗皮肤癌。
项目成果
期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Real-time visualization of photochemically induced fluorescence of 8-halogenated quinolones: lomefloxacin, clinafloxacin and Bay3118 in live human HaCaT keratinocytes.
活人 HaCaT 角质形成细胞中 8-卤代喹诺酮类药物洛美沙星、克那沙星和 Bay3118 光化学诱导荧光的实时可视化。
- DOI:10.1111/j.1751-1097.2010.00741.x
- 发表时间:2010
- 期刊:
- 影响因子:3.3
- 作者:Koker,EdmondB;Bilski,PiotrJ;Motten,AnnG;Zhao,Baozhong;Chignell,ColinF;He,Yu-Ying
- 通讯作者:He,Yu-Ying
UVA induces lesions resembling seborrheic keratoses in mice with keratinocyte-specific PTEN downregulation.
UVA 会在角质形成细胞特异性 PTEN 下调的小鼠中诱导类似脂溢性角化病的病变。
- DOI:10.1038/jid.2011.33
- 发表时间:2011
- 期刊:
- 影响因子:0
- 作者:Ming,Mei;Shea,ChristopherR;Feng,Li;Soltani,Keyoumars;He,Yu-Ying
- 通讯作者:He,Yu-Ying
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Yu-Ying He其他文献
Yu-Ying He的其他文献
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{{ truncateString('Yu-Ying He', 18)}}的其他基金
Epitranscriptomic mechanism of environmental stress response and tumorigenesis
环境应激反应与肿瘤发生的表观转录组机制
- 批准号:
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- 资助金额:
$ 36.49万 - 项目类别:
FTO and RNA methylation in arsenic tumorigenicity
FTO 和 RNA 甲基化在砷致瘤性中的作用
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FTO and RNA methylation in arsenic tumorigenicity
FTO 和 RNA 甲基化在砷致瘤性中的作用
- 批准号:
10454271 - 财政年份:2020
- 资助金额:
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The mechanistic role of METTL14 in UVB-induced skin tumorigenesis
METTL14在UVB诱导的皮肤肿瘤发生中的机制作用
- 批准号:
10541839 - 财政年份:2019
- 资助金额:
$ 36.49万 - 项目类别:
The mechanistic role of METTL14 in UVB-induced skin tumorigenesis
METTL14在UVB诱导的皮肤肿瘤发生中的机制作用
- 批准号:
9904648 - 财政年份:2019
- 资助金额:
$ 36.49万 - 项目类别:
The mechanistic role of METTL14 in UVB-induced skin tumorigenesis
METTL14在UVB诱导的皮肤肿瘤发生中的机制作用
- 批准号:
9751010 - 财政年份:2019
- 资助金额:
$ 36.49万 - 项目类别:
The mechanistic role of METTL14 in UVB-induced skin tumorigenesis
METTL14在UVB诱导的皮肤肿瘤发生中的机制作用
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10320925 - 财政年份:2019
- 资助金额:
$ 36.49万 - 项目类别:
Autophagy and GG-NER in UVB-induced skin cancer
UVB 诱导的皮肤癌中的自噬和 GG-NER
- 批准号:
8887808 - 财政年份:2015
- 资助金额:
$ 36.49万 - 项目类别:
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- 批准号:
10404014 - 财政年份:2015
- 资助金额:
$ 36.49万 - 项目类别:
YTHDF2 and UVB damage response in skin cancer
皮肤癌中的 YTHDF2 和 UVB 损伤反应
- 批准号:
10614617 - 财政年份:2015
- 资助金额:
$ 36.49万 - 项目类别:
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