TY - JOUR
T1 - Identification of the dopamine transporter SLC6A3 as a biomarker for patients with renal cell carcinoma
AU - Schrödter, Sarah
AU - Braun, Martin
AU - Syring, Isabella
AU - Klümper, Niklas
AU - Deng, Mario
AU - Schmidt, Doris
AU - Perner, Sven
AU - Müller, Stefan C.
AU - Ellinger, Jörg
N1 - Publisher Copyright:
© 2016 Schrödter et al.
Copyright:
Copyright 2016 Elsevier B.V., All rights reserved.
PY - 2016/2/2
Y1 - 2016/2/2
N2 - Background: Clear cell renal cell carcinoma (ccRCC) is among the most common human malignancies. Methods: In 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. Results: Differential 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. Conclusion: Our study identified several novel biomarkers with diagnostic potential and further investigations on sertraline as therapeutic agent in ccRCC patients are warranted.
AB - Background: Clear cell renal cell carcinoma (ccRCC) is among the most common human malignancies. Methods: In 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. Results: Differential 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. Conclusion: Our study identified several novel biomarkers with diagnostic potential and further investigations on sertraline as therapeutic agent in ccRCC patients are warranted.
UR - http://www.scopus.com/inward/record.url?scp=84956736328&partnerID=8YFLogxK
U2 - 10.1186/s12943-016-0495-5
DO - 10.1186/s12943-016-0495-5
M3 - Journal articles
C2 - 26831905
AN - SCOPUS:84956736328
VL - 15
JO - Molecular Cancer
JF - Molecular Cancer
IS - 1
M1 - 10
ER -
