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Overexpression of functional SLC6A3 in clear cell renal cell carcinoma

Author:
  • Jennifer Hansson
  • David Lindgren
  • Helén Nilsson
  • Elinn Johansson
  • Martin Johansson
  • Lena Gustavsson
  • Håkan Axelson
Publishing year: 2017
Language: English
Pages: 2105-2115
Publication/Series: Clinical Cancer Research
Volume: 23
Issue: 8
Document type: Journal article
Publisher: American Association for Cancer Research

Abstract english

PURPOSE: Renal cell carcinoma (RCC) is derived from a tissue with a remarkable capacity for vectorial transport. We therefore performed an unbiased exploration of transporter proteins in normal kidney and kidney cancer in order to discover novel clinical targets.

EXPERIMENTAL DESIGN: Using the TCGA database we investigated differences in membrane transporter expression in ccRCC and normal kidney. We identified the dopamine transporter SLC6A3 as a specific biomarker for ccRCC. To investigate the functionality of SLC6A3 we used a [3H]-dopamine uptake assay on ccRCC cells. We further explored the effect of HIF proteins on SLC6A3 expression by introducing siRNA in ccRCC cells and by hypoxic treatment of non-malignant cells.

RESULTS: We show that ccRCC express very high transcript levels of SLC6A3 in contrast to normal kidney tissue and other tumor types, which do not express appreciable levels of this transporter. Importantly, we demonstrate that the elevated expression of SLC6A3 in ccRCC cells is associated with specific uptake of dopamine. By targeting the expression of HIF-1α and HIF-2α we could show that SLC6A3 expression is primarily influenced by HIF-2α, and that hypoxia can induce SLC6A3 expression in normal renal cells.

CONCLUSIONS: We conclude that the dopamine transporter SLC6A3 constitute a novel biomarker that is highly specific for ccRCC. We further postulate that the protein can be exploited for diagnostic or therapeutic purposes for detection or treatment of ccRCC.

Keywords

  • Cell and Molecular Biology

Other

Published
  • Clinical pathology, Malmö
  • Kidney cancer research group
  • ISSN: 1078-0432
Håkan Axelson
E-mail: hakan [dot] axelson [at] med [dot] lu [dot] se

Professor

Division of Translational Cancer Research

+46 46 222 64 34

MV 404 A31A2

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