We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Variant G6PD levels promote tumor cell proliferation or apoptosis via the STAT3/5 pathway in the human melanoma xenograft mouse model.
- Authors
Tao Hu; Chunhua Zhang; Qiongling Tang; Yanan Su; Bo Li; Long Chen; Zheng Zhang; Tianchi Cai; Yuechun Zhu; Hu, Tao; Zhang, Chunhua; Tang, Qiongling; Su, Yanan; Li, Bo; Chen, Long; Zhang, Zheng; Cai, Tianchi; Zhu, Yuechun
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>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.
- Subjects
CANCER cell proliferation; GLUCOSE 6-phosphatase; APOPTOSIS; MELANOMA; MELANOCYTES; XENOGRAFTS
- Publication
BMC Cancer, 2013, Vol 13, Issue 1, p1
- ISSN
1471-2407
- Publication type
journal article
- DOI
10.1186/1471-2407-13-251