Variant G6PD levels promote tumor cell proliferation or apoptosis via the STAT3/5 pathway in the human melanoma xenograft mouse model.
Variant G6PD levels promote tumor cell proliferation or apoptosis via the STAT3/5 pathway in the human melanoma xenograft mouse model.
复制标题
在人黑色素瘤异种移植小鼠模型中，变体 G6PD 水平通过 STAT3/5 途径促进肿瘤细胞增殖或凋亡
DOI：
10.1186/1471-2407-13-251
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发表时间：
2013-05-22
期刊：
影响因子：
3.8
通讯作者：
Zhu Y
中科院分区：
文献类型：
--
作者：
Hu T;Zhang C;Tang Q;Su Y;Li B;Chen L;Zhang Z;Cai T;Zhu Y
研究背景葡萄糖-6-磷酸脱氢酶（G6 PD）是戊糖-磷酸途径中的第一个反应酶，在肿瘤细胞中表达增高。G6 PD在人黑色素瘤生长中的调控机制和病理变化尚不清楚（人表皮黑素细胞）细胞和具有野生型G6 PD基因（A375-WT）、G6 PD缺陷的人黑素瘤细胞（A375-G6 PD），G6 PD cDNA过表达将突变型G6 PD cDNA（A375-G6 PD α-G6 PD-WT）和突变型G6 PD cDNA（A375-G6 PD α-G6 PD-G487 A）皮下注射到5组裸鼠中。通过实时定量PCR、免疫组化和westernblot检测G6 PD、STAT 3、STAT 5、细胞周期相关蛋白和凋亡蛋白的表达，并探讨STAT 3/STAT 5的作用机制。在A375-G6 PD诱导的肿瘤组织中观察到G6 PD表达和活性显著降低，沿着下调的细胞周期蛋白cyclin D1、cyclin E、p53和S100 A4。与A375-WT细胞相比，凋亡抑制因子Bcl-2和Bcl-xl表达上调，而凋亡因子Fas表达下调。结论G6 PD可能通过磷酸化转录因子STAT 3和STAT 5，调控细胞凋亡和细胞周期相关蛋白的表达，从而介导人黑色素瘤细胞的形成和生长。然而，还需要进一步的研究来确定潜在的临床应用。
BackgroundGlucose-6-phosphate dehydrogenase (G6PD), elevated in tumor cells, catalyzes the first reaction in the pentose-phosphate pathway. The regulation mechanism of G6PD and pathological change in human melanoma growth remains unknown.MethodsHEM (human epidermal melanocyte) cells and human melanoma cells with the wild-typeG6PDgene (A375-WT), G6PD deficiency (A375-G6PD∆), G6PD cDNA overexpression (A375-G6PD∆-G6PD-WT), and mutant G6PD cDNA (A375-G6PD∆-G6PD-G487A) were subcutaneously injected into 5 groups of nude mice. Expressions of G6PD, STAT3, STAT5, cell cycle-related proteins, and apoptotic proteins as well as mechanistic exploration of STAT3/STAT5 were determined by quantitative real-time PCR (qRT-PCR), immunohistochemistry and western blot.ResultsDelayed formation and slowed growth were apparent in A375-G6PD∆ cells, compared to A375-WT cells. Significantly decreased G6PD expression and activity were observed in tumor tissues induced by A375-G6PD∆, along with down-regulated cell cycle proteins cyclin D1, cyclin E, p53, and S100A4. Apoptosis-inhibited factors Bcl-2 and Bcl-xl were up-regulated; however, apoptosis factor Fas was down-regulated, compared to A375-WT cells. Moderate protein expressions were observed in A375-G6PD∆-G6PD-WT and A375-G6PD∆-G6PD-G487A cells.ConclusionsG6PD may regulate apoptosis and expression of cell cycle-related proteins through phosphorylation of transcription factors STAT3 and STAT5, thus mediating formation and growth of human melanoma cells. Further study will, however, be required to determine potential clinical applications.
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影响因子：
11.2
作者：
Manuel ER;Blache CA;Paquette R;Kaltcheva TI;Ishizaki H;Ellenhorn JD;Hensel M;Metelitsa L;Diamond DJ
通讯作者：
Diamond DJ
影响因子：
6.4
作者：
Langbein, Sigrun;Frederiks, Wilma M.;Coy, Johannes F.
通讯作者：
Coy, Johannes F.
影响因子：
9.7
作者：
Batetta, B;Pulisci, D;Dessì, S
通讯作者：
Dessì, S
影响因子：
15.9
作者：
Bromberg, J
通讯作者：
Bromberg, J
影响因子：
1.1
作者：
Bergman, R;Shemer, A;Lichtig, C
通讯作者：
Lichtig, C