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Open Access Highly Accessed Research article

Variant G6PD levels promote tumor cell proliferation or apoptosis via the STAT3/5 pathway in the human melanoma xenograft mouse model

Tao Hu12, Chunhua Zhang13, Qiongling Tang14, Yanan Su5, Bo Li6, Long Chen1, Zheng Zhang1, Tianchi Cai1 and Yuechun Zhu1*

Author Affiliations

1 Department of Biochemistry and Molecular Biology, Kunming Medical University, Kunming 650031, China

2 Department of laboratory medicine, The Third People’s Hospital of Yunnan Province, Kunming, China

3 Yunnan Provincial Maternal and Child Health Hospital, Kunming, China

4 Shenzhen Luohu Maternal and Child Health Hospital, Shenzhen, China

5 GenProMarkers, Inc., 9700 Great Seneca Highway, Suite182, Rockville, MD 20850, USA

6 Department of laboratory animal, Kunming Medical University, Kunming, China

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BMC Cancer 2013, 13:251  doi:10.1186/1471-2407-13-251

Published: 22 May 2013

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.

Keywords:
Glucose-6-phosphate dehydrogenase; Melanoma; Nude mice; Apoptosis; Signal transduction and transcription activator