Identification of the dopamine transporter SLC6A3 as a biomarker for patients with renal cell carcinoma

Molecular Cancer

Research

Stefan C Müller¹  Doris Schmidt¹  Sarah Schrödter¹  Jörg Ellinger²  Isabella Syring³  Martin Braun⁴  Sven Perner⁴  Niklas Klümper⁴  Mario Deng⁵ 

[1] Department of Urology, University Hospital Bonn, Bonn, Germany;Department of Urology, University Hospital Bonn, Bonn, Germany;Klinik und Poliklinik für Urologie und Kinderurologie, Universitätsklinikum Bonn, Sigmund-Freud-Strasse 25, 53105, Bonn, Germany;Department of Urology, University Hospital Bonn, Bonn, Germany;Section for Prostate Cancer Research, Institute of Pathology, Center for Integrated Oncology, University Hospital Bonn, Cologne/Bonn, Germany;Section for Prostate Cancer Research, Institute of Pathology, Center for Integrated Oncology, University Hospital Bonn, Cologne/Bonn, Germany;Section for Prostate Cancer Research, Institute of Pathology, Center for Integrated Oncology, University Hospital Bonn, Cologne/Bonn, Germany;Klinik und Poliklinik für Urologie und Kinderurologie, Universitätsklinikum Bonn, Sigmund-Freud-Strasse 25, 53105, Bonn, Germany;

关键词: Renal cell carcinoma;    SLC6A3;    Expression profiling;    Biomarker;    Microarray;    Sertraline;   

DOI  :  10.1186/s12943-016-0495-5

 received in 2015-08-05, accepted in 2016-01-27,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundClear cell renal cell carcinoma (ccRCC) is among the most common human malignancies.MethodsIn order to provide better understanding of the molecular biology of ccRCC and to identify potential diagnostic/prognostic biomarker and therapeutic targets, we utilized a microarray to profile mRNA expression of corresponding normal and malignant renal tissues. Real-time PCR, Western Blot and immunohistochemistry were applied to study the expression of candidate biomarkers. ccRCC cell lines were treated with sertraline to inhibit the dopamine transporter SLC6A3.ResultsDifferential expression of fourteen mRNAs, yet not studied in ccRCC in depth, was confirmed using qPCR (upregulation: SLC6A3, NPTX2, TNFAIP6, NDUFA4L2, ENPP3, FABP6, SPINK13; downregulation: FXYD4, SLC12A1, KNG1, NPHS2, SLC13A3, GCGR, PLG). Up-/downregulation was also confirmed for FXYD4, KNG1, NPTX2 and SLC12A1 by Western Blot on the protein level. In contrast to the mRNA expression, protein expression of the dopamine transporter SLC6A3 was lower in ccRCC compared to normal renal tissue. Immunohistochemistry indicated that this decrease was due to higher concentrations of SLC6A3 in the proximal tubules. Immunohistochemical analyses further demonstrated that high SLC6A3 expression in ccRCC tissue was correlated with a shorter period of recurrence-free survival following surgery. Treatment of ccRCC cells with the SLC6A3 inhibitor sertraline induced dose-dependent cell-death.ConclusionOur study identified several novel biomarkers with diagnostic potential and further investigations on sertraline as therapeutic agent in ccRCC patients are warranted.

【 授权许可】

CC BY   
© Schrödter et al. 2016