title: Variant G6PD levels promote tumor cell proliferation or apoptosis via the STAT3/5 pathway in the human melanoma xenograft mouse model.
abstract: BACKGROUND
  Glucose-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.
  
  
  METHODS
  HEM (human epidermal melanocyte) cells and human melanoma cells with the wild-type G6PD gene (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.
  
  
  RESULTS
  Delayed 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.
  
  
  CONCLUSIONS
  G6PD 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Kunming Medical University, Kunming 650031, China. Zhuyuechun20091119@126.com.
authors.forename: Tao
authors.initials: T
authors.lastname: Hu
authors.forename: Chunhua
authors.initials: C
authors.lastname: Zhang
authors.forename: Qiongling
authors.initials: Q
authors.lastname: Tang
authors.forename: Yanan
authors.initials: Y
authors.lastname: Su
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.forename: Long
authors.initials: L
authors.lastname: Chen
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Tianchi
authors.initials: T
authors.lastname: Cai
authors.forename: Yuechun
authors.initials: Y
authors.lastname: Zhu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004195:Disease Models, Animal; D004789:Enzyme Activation; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D014644:Genetic Variation; D005954:Glucosephosphate Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D064593:Heterografts; D006801:Humans; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D050799:STAT5 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; D005954:Glucosephosphate Dehydrogenase