Universität zu Köln

Schroedter, Sarah, Braun, Martin, Syring, Isabella, Kluemper, Niklas, Deng, Mario, Schmidt, Doris, Perner, Sven, Mueller, Stefan C. and Ellinger, Joerg (2016). Identification of the dopamine transporter SLC6A3 as a biomarker for patients with renal cell carcinoma. Mol. Cancer, 15. LONDON: BMC. ISSN 1476-4598

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Abstract

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Schroedter, Sarah UNSPECIFIED UNSPECIFIED UNSPECIFIED Braun, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Syring, Isabella UNSPECIFIED UNSPECIFIED UNSPECIFIED Kluemper, Niklas UNSPECIFIED UNSPECIFIED UNSPECIFIED Deng, Mario UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmidt, Doris UNSPECIFIED UNSPECIFIED UNSPECIFIED Perner, Sven UNSPECIFIED UNSPECIFIED UNSPECIFIED Mueller, Stefan C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ellinger, Joerg UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-284811
DOI:	10.1186/s12943-016-0495-5
Journal or Publication Title:	Mol. Cancer
Volume:	15
Date:	2016
Publisher:	BMC
Place of Publication:	LONDON
ISSN:	1476-4598
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GENE-EXPRESSION; MESSENGER-RNA; CANCER; PROTEINS Multiple languages Biochemistry & Molecular Biology; Oncology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/28481