Hematopoietic- and neurologic-expressed sequence 1 (Hn1) depletion in B16.F10 melanoma cells promotes a differentiated phenotype that includes increased melanogenesis and cell cycle arrest.
Hematopoietic- and neurologic-expressed sequence 1 (Hn1) depletion in B16.F10 melanoma cells promotes a differentiated phenotype that includes increased melanogenesis and cell cycle arrest.
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DOI：
10.1016/j.diff.2009.04.001
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发表时间：
2009-07
期刊：
影响因子：
2.9
通讯作者：
Harrison, Jeffrey K.
中科院分区：
文献类型：
--
作者：
Laughlin, Katharine M.;Luo, Defang;Liu, Che;Shaw, Gerry;Warrington, Kenneth H., Jr.;Law, Brian K.;Harrison, Jeffrey K.
造血和神经表达序列1(Hn1)基因编码一种在物种间高度保守的小蛋白。Hn1在再生的神经组织中表达上调，包括成年啮齿类动物的面运动神经和去分化的视网膜色素上皮细胞。它也在胚胎发育过程中的许多组织中表达，以及在成年大脑中表现出高可塑性的区域表达。Hn1也被报道为人类卵巢癌的标志物，它在高级别的人脑胶质瘤中表达。本研究旨在了解Hn1在小鼠黑色素瘤细胞系中的功能。在B16-F10细胞及其形成的肿瘤中检测到Hn1基因和蛋白的表达。用siRNA抑制Hn1蛋白的表达可增加黑素合成。HN1缺失的细胞表达更高水平的黑素生成蛋白酪氨酸酶和Trp2，并增加了肌动蛋白和Rab27a之间的相互作用。由于G1/S细胞周期停滞，Hn1耗竭细胞的体外生长速度明显降低。这与视网膜母细胞瘤蛋白的磷酸化减少以及p27水平的降低和p21的表达增加是一致的。肝细胞生长因子受体c-Met的表达也在Hn1缺失的细胞中被检测到，但依赖于HGF的磷酸化ERK的刺激不受影响。HN1缺失还导致基础水平的磷酸化p38MAPK升高，而基础ERK磷酸化水平降低。此外，Hn1缺失的细胞转录因子MITF和USF-1的表达减少，TFE3的表达增加。这些数据，再加上关于Hn1在再生和发育过程中表达的报道，表明Hn1在修复或增殖的细胞中起着分化抑制的作用。
The Hematopoietic- and neurologic-expressed sequence 1 (Hn1) gene encodes a small protein that is highly conserved among species. Hn1 expression is upregulated in regenerating neural tissues, including the axotomized adult rodent facial motor nerve and dedifferentiating retinal pigment epithelial cells of the Japanese newt. It is also expressed in numerous tissues during embryonic development as well as in regions of the adult brain that exhibit high plasticity. Hn1 has also been reported as a marker for human ovarian carcinoma and it is expressed in high-grade human gliomas. This study was directed toward understanding the function of Hn1 in a murine melanoma cell line. Hn1 mRNA and protein were identified in B16.F10 cells and in tumors formed from these cells. Inhibition of Hn1 protein expression with siRNA increased melanogenesis. Hn1-depleted cells expressed higher levels of the melanogenic proteins tyrosinase and Trp2 and an increased interaction between actin and Rab27a. The in vitro cell growth rate of Hn1-depleted cells was significantly reduced due to G1/S cell cycle arrest. This was consistent with a reduction in the phosphorylation of retinoblastoma protein as well as lower levels of p27 and increased expression of p21. Decreased expression of c-Met, the receptor for hepatocyte growth factor, was also detected in the Hn1-depleted cells, however HGF-dependent stimulation of phosphorylated-ERK was unaffected. Hn1 depletion also led to increased basal levels of phosphorylated p38 MAPK, while basal ERK phosphorylation was reduced. Moreover, Hn1-depleted cells had reduced expression of transcription factors MITF and USF-1, and increased expression of TFE3. These data, coupled with reports on Hn1 expression in regeneration and development, suggest that Hn1 functions as a suppressor of differentiation in cells undergoing repair or proliferation.
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DOI：
10.1038/newbio242148a0
发表时间：
1973-01-01
期刊：
NATURE-NEW BIOLOGY
影响因子：
--
作者：
FIDLER, IJ
通讯作者：
FIDLER, IJ
影响因子：
3.7
作者：
Wellbrock C;Rana S;Paterson H;Pickersgill H;Brummelkamp T;Marais R
通讯作者：
Marais R
影响因子：
2.5
作者：
Tang, WZ;Lai, YH;Chui, DHK
通讯作者：
Chui, DHK
影响因子：
5.1
作者：
McCarty, DM;Monahan, PE;Samulski, RJ
通讯作者：
Samulski, RJ
DOI：
10.1111/j.1600-0749.2006.00348.x
发表时间：
2006-12-01
期刊：
PIGMENT CELL RESEARCH
影响因子：
--
作者：
Saha, Bidisha;Singh, Suman Kumar;Bhadra, Ranjan
通讯作者：
Bhadra, Ranjan