Id1 delays senescence of primary human melanocytes.-猫眼课题宝

DOI：

10.1002/mc.20422

发表时间：

2008-09

期刊：

MOLECULAR CARCINOGENESIS

影响因子：

4.6

通讯作者：

中科院分区：

医学2区

文献类型：

作者：

Cummings, Staci D.;Ryu, Byungwoo;Samuels, Michael A.;Yu, Xiaobing;Meeker, Alan K.;Healey, Megan A.;Alani, Rhoda M.

关键词：

melanocyte Id1 senescence

来源链接：

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4066980/?report=classic

Id家族的螺旋-环-螺旋转录因子在多种人类恶性肿瘤中上调，并通过影响细胞生长、分化和肿瘤血管生成而参与促进肿瘤发生。虽然Id蛋白的表达与肿瘤发生有关，但Id表达与癌发生之间的确切机制关系尚未明确。我们以前已经表明，Id 1通过抑制细胞周期调节蛋白和家族性黑色素瘤基因p16/INK 4a来延迟原代哺乳动物细胞的细胞衰老。我们还表明，Id 1表达上调，在早期原发性人类黑色素瘤，并可能是一个重要的标志物，早期恶性肿瘤。为了进一步确定Id 1在人黑色素瘤发展中的作用，我们评估了Id 1在原代人黑色素细胞中的功能。在这里，我们表明，组成型表达的Id 1在原代人类黑素细胞导致细胞衰老延迟和家族性黑色素瘤基因，p16/INK 4a的表达降低。虽然黑素细胞组成性表达Id 1显示具有延长的寿命，这是不相关的细胞生长或端粒长度的明显变化。我们的结论是，Id 1通过抑制p16/INK 4a的表达，延迟细胞衰老的原代人黑素细胞，并建议，Id 1可能有助于通过延长细胞寿命的原代人黑素细胞的恶性转化。

The Id family of helix-loop-helix transcription factors is upregulated in a variety of human malignancies and has been implicated in promoting tumorigenesis through effects on cell growth, differentiation, and tumor angiogenesis. While expression of Id proteins has been associated with tumorigenesis, the precise mechanistic relationship between Id expression and carcinogenesis has not been clearly delineated. We have previously shown that Id1 delays cellular senescence in primary mammalian cells through inhibition of the cell cycle regulatory protein and familial melanoma gene, p16/INK4a. We have also demonstrated that Id1 expression is upregulated in early stage primary human melanomas and may be an important marker for early malignancy. In order to further define the role of Id1 in human melanoma development, we have evaluated the function of Id1 in primary human melanocytes. Here we show that constitutive expression of Id1 in primary human melanocytes leads to delayed cellular senescence and decreased expression of the familial melanoma gene, p16/INK4a. Although melanocytes constitutively expressing Id1 are shown to possess extended lifespans, this is not associated with an appreciable change in cell growth or telomere length. We conclude that Id1 delays cellular senescence in primary human melanocytes through inhibition of p16/INK4a expression and suggest that Id1 may contribute to the malignant conversion of primary human melanocytes through extension of cellular lifespan.