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Tyrosine kinase expression profile in clear cell renal cell carcinoma

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Abstract

Purpose

To profile different tyrosine kinase (TK) expression patterns in clear cell renal carcinoma (ccRCC).

Methods

We analysed mRNA expression levels of 89 receptor and non-receptor TK in corresponding cancer and normal renal tissue from 5 patients with ccRCC using the TaqMan Low-Density Array technology. In order to confirm aberrant TK expressions, a subsequent analysis of 25 ccRCC and corresponding normal renal tissues was performed, applying quantitative real-time PCR. To confirm mRNA expression levels on protein level, we studied ERBB4 and HCK using immunohistochemistry.

Results

A total of 12 TK were significantly upregulated in ccRCC (ABL2, FLT1, BTK, HCK, JAK3, CSF1R, MET, JAK1, MATK, PTPRC, FYN and CSK), coherently 7 TK demonstrated a down-regulation (ERBB4, PDGFRA, NRTK3, SYK, ERBB2, FGFR3 and PTK7). These findings were validated by the utilization of RT-PCR for ABL2, FLT1 BTK, HCK, JAK3, CSF1R, MET, JAK1, MATK and vice versa for ERBB4 and PDGFRA. Immunohistochemistry revealed ERBB4 expression to be significantly lower in ccRCC in comparison to papillary RCC, chromophobe RCC, renal oncocytoma and normal renal tissue (P < 0.001). HCK protein expression was reduced in ccRCC in contrast to papillary RCC (P < 0.001) or oncocytoma (P = 0.023), but similar to chromphobe RCC (P = 0.470), sarcomatoid RCC (P = 0.754) and normal renal tissue (P = 0.083). Neither ERBB4 nor HCK were correlated (P > 0.05) with clinical–pathological parameters.

Conclusion

TK constitute valuable targets for pharmaceutical anti-cancer therapy. ERBB4 and HCK depict significantly lower expression levels in renal cancer tissues.

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Acknowledgments

We thank Doris Schmidt for technical assistance.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Klinik und Poliklinik für Urologie und Kinderurologie, Universitätsklinikum Bonn, Sigmund-Freud-Strasse 25, 53105, Bonn, Germany

    Turang E. Behbahani, Claudia Thierse, Claudia Baumann, Daniel Holl, Stefan C. Müller, Jörg Ellinger & Stefan Hauser

  2. Institut für Pathologie, Universitätsklinikum Bonn, Bonn, Germany

    Alexander von Ruecker

  3. Urologische Klinik und Poliklinik, Universitätsklinikum München-Großhadern, Munich, Germany

    Patrick J. Bastian

Authors
  1. Turang E. Behbahani
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  2. Claudia Thierse
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  3. Claudia Baumann
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  4. Daniel Holl
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  5. Patrick J. Bastian
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Corresponding authors

Correspondence to Jörg Ellinger or Stefan Hauser.

Additional information

Jörg Ellinger and Stefan Hauser are contributed equally to this work.

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Behbahani, T.E., Thierse, C., Baumann, C. et al. Tyrosine kinase expression profile in clear cell renal cell carcinoma. World J Urol 30, 559–565 (2012). https://doi.org/10.1007/s00345-011-0767-z

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  • DOI: https://doi.org/10.1007/s00345-011-0767-z

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