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Androgens enhance the glycolytic metabolism and lactate export in prostate cancer cells by modulating the expression of GLUT1, GLUT3, PFK, LDH and MCT4 genes

  • Original Article – Cancer Research
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Abstract

Purpose

The present study aims to investigate the role of androgens in controlling the glycolytic metabolism and lactate efflux in prostate cancer (PCa) cells.

Methods

Androgen-responsive LNCaP cells were treated with 5α-dihydrotestosterone (DHT, 10 nM) for 12–48 h, and their glycolytic metabolism, lactate production and viability were analyzed. Intracellular and extracellular levels of glucose and lactate were determined spectrophotometrically, and the expression of glucose transporters (GLUT1/GLUT3), phosphofructokinase 1, lactate dehydrogenase (LDH) and monocarboxylate transporter (MCT4) was analyzed by real-time PCR and Western blot. The enzymatic activity of LDH was determined by means of a colorimetric assay. Experiments were reproduced in androgen-non-responsive DU145 and PC3 cells.

Results

Androgens stimulated glucose consumption in LNCaP cells by increasing the expression of GLUT3, GLUT1 and PFK, which was underpinned by increased cell viability. Accordingly, lactate production by LNCaP cells was enhanced upon DHT stimulation as evidenced by the increased levels of lactate found in cell culture medium. Although LDH enzymatic activity decreased in LNCaP cells treated with DHT, the expression of MCT4 was significantly increased with androgenic treatment, which sustains the increase on lactate export. Glucose consumption and the expression of GLUTs and PFK remained unchanged in DHT-treated DU145 and PC3 cells.

Conclusions

The results obtained establish androgens as modulators of glycolytic metabolism in PCa cells by stimulating glucose consumption, as well as the production and export of lactate, which may represent a crucial issue-driven prostate tumor development. These findings also highlight the importance of PCa therapies targeting AR and metabolism-related proteins.

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Acknowledgments

This work was partially supported by the Pluriannual Programme of Portuguese Foundation for Science and Technology (FCT) under Program COMPETE (PEst-OE/SAU/UI0709/2014). Pedro F. Oliveira was financed by FCT under the program Ciência 2008. Cátia Vaz, Ricardo Marques and Marco Alves were funded by FCT fellowships (SFRH/BD/70316/2010, SFRH/BD/66875/2009 and SRFH/BPD/80451/2011, respectively).

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We declare that we have no conflict of interest.

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Authors and Affiliations

  1. Faculdade de Ciências da Saúde, CICS-UBI - Health Sciences Research Centre, University of Beira Interior, Av. Infante D. Henrique, 6200-506, Covilhã, Portugal

    Cátia V. Vaz, Ricardo Marques, Marco G. Alves, Pedro F. Oliveira, José E. Cavaco, Cláudio J. Maia & Sílvia Socorro

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  1. Cátia V. Vaz
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  2. Ricardo Marques
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Correspondence to Sílvia Socorro.

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Vaz, C.V., Marques, R., Alves, M.G. et al. Androgens enhance the glycolytic metabolism and lactate export in prostate cancer cells by modulating the expression of GLUT1, GLUT3, PFK, LDH and MCT4 genes. J Cancer Res Clin Oncol 142, 5–16 (2016). https://doi.org/10.1007/s00432-015-1992-4

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  • DOI: https://doi.org/10.1007/s00432-015-1992-4

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