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Håkan Axelson

Håkan Axelson

Research team manager

Håkan Axelson

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

Summary, in 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.

Department/s

  • Kidney cancer research group
  • Division of Translational Cancer Research
  • Clinical pathology, Malmö
  • BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation

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

Topic

  • Cell and Molecular Biology

Status

Published

Research group

  • Kidney cancer research group
  • Clinical pathology, Malmö

ISBN/ISSN/Other

  • ISSN: 1078-0432