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Updated: May 28, 2026

The Use of Reverse Phase Protein Arrays (RPPA) to Explore Protein Expression Variation within Individual Renal Cell Cancers
Published on: January 22, 2013
Tyrosine kinase expression profile in clear cell renal cell carcinoma
Turang E Behbahani1, Claudia Thierse, Claudia Baumann
1Klinik und Poliklinik für Urologie und Kinderurologie, Universitätsklinikum Bonn, Sigmund-Freud-Strasse 25, Bonn, Germany.
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.
Insights
Tyrosine kinases (TK) show altered expression in clear cell renal carcinoma (ccRCC). ERBB4 and HCK were significantly downregulated in ccRCC, indicating their potential as therapeutic targets.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Clear cell renal carcinoma (ccRCC) is the most common subtype of kidney cancer.
- Understanding the molecular mechanisms, including protein expression patterns, is crucial for developing targeted therapies.
- Tyrosine kinases (TKs) play significant roles in cell signaling pathways implicated in cancer development and progression.
Purpose of the Study:
- To comprehensively profile the expression patterns of various tyrosine kinases (TKs) in ccRCC.
- To identify specific TKs that are differentially expressed in ccRCC compared to normal renal tissue.
- To investigate the potential of these TKs as therapeutic targets for ccRCC treatment.
Main Methods:
- Analysis of mRNA expression levels for 89 TKs in ccRCC and normal renal tissues using TaqMan Low-Density Array.
- Validation of aberrant TK expressions using quantitative real-time PCR (qRT-PCR).
- Confirmation of protein expression levels for ERBB4 and HCK via immunohistochemistry.
Main Results:
- Twelve TKs were significantly upregulated in ccRCC, while seven TKs, including ERBB4 and PDGFRA, were downregulated.
- Validation by qRT-PCR confirmed the differential expression of several TKs.
- Immunohistochemistry showed significantly lower ERBB4 and HCK protein expression in ccRCC compared to other renal tumor subtypes and normal tissue.
Conclusions:
- Tyrosine kinases represent promising targets for pharmaceutical anti-cancer therapy in ccRCC.
- Significantly reduced expression of ERBB4 and HCK in renal cancer tissues suggests their potential as biomarkers or therapeutic targets.
- Further research into the functional roles of ERBB4 and HCK in ccRCC pathogenesis is warranted.
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