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Published on: November 3, 2013
Gene expression profiling of ERBB receptors and ligands in human transitional cell carcinoma of the bladder
Delphine Amsellem-Ouazana1, Ivan Bièche, Sengül Tozlu
1Department of Urology, Hôpital Cochin, Paris, France. d.amsellem-ouazana@cch.aphp-paris.fr
Purpose:
The ErbB driven growth pathway has been implicated in most human epithelial malignancies. Therefore, its blockade is a promising therapeutic strategy and several candidate drugs are currently undergoing clinical trials. Paradoxically little is known of the expression pattern or clinical significance of the 4 ErbB receptors and their 11 ligands in TCC of the bladder.
Materials And Methods:
To obtain further insight into the molecular pathogenesis of TCC we used quantitative real-time reverse transcriptase-polymerase chain reaction assay to quantify mRNA expression of the 4 ERBB and their 11 known ligand genes, including recently described EPGN/epigen, in 73 tumor samples.
Results:
The level of mRNA of 4 ligand genes (EGF, NRG1, NRG2 and NRG3) was extremely low, that is detectable but not quantifiable. Six genes were over expressed (ERBB2, TGFA, HB-EGF, AREG, EREG and EPGN), 3 were under expressed (ERBB1, ERBB4 and NRG4) and 2 were over or under expressed (ERBB3 and BTC). ERBB2 and AREG expression differed between early stage tumors (pTa grade 1) and normal samples. The most marked differences in expression were ERBB3, EREG and NRG4 between superficial and muscle invasive tumors (p = 0.0069, 0.00007 and 0.0000001, respectively), and TGFA and NRG4 between low and high grade superficial tumors, and between pT1 or greater and pTa tumors.
Conclusions:
This study shows the involvement of the ERBB family and ligand genes in TCC. Most receptor and ligand genes are deregulated at different stages of carcinogenesis, implying that they should be studied simultaneously. Quantitative real-time reverse transcriptase-polymerase chain reaction could be used to determine ErbB signaling pathway status in individuals with a view to tailored therapy.
Insights
The ErbB signaling pathway is involved in bladder cancer, with several receptor and ligand genes showing altered expression. This suggests potential for targeted therapies based on individual ErbB pathway status.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The ErbB signaling pathway is crucial in epithelial malignancies.
- Targeting ErbB is a promising therapeutic strategy for cancers.
- Expression patterns of ErbB receptors and ligands in bladder cancer are poorly understood.
Purpose of the Study:
- To investigate the expression patterns of ErbB receptors and their ligands in urothelial carcinoma (TCC) of the bladder.
- To determine the clinical significance of ErbB signaling in bladder cancer pathogenesis.
Main Methods:
- Quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) was used.
- mRNA expression of 4 ErbB receptors and 11 known ligand genes was quantified.
- 73 tumor samples were analyzed.
Main Results:
- Six genes (ERBB2, TGFA, HB-EGF, AREG, EREG, EPGN) were overexpressed, and three (ERBB1, ERBB4, NRG4) were underexpressed.
- ERBB2 and AREG expression differed between early-stage tumors and normal tissue.
- Significant differences in ERBB3, EREG, and NRG4 expression were observed between superficial and muscle-invasive tumors.
Conclusions:
- The ErbB family and ligand genes are implicated in urothelial carcinoma (TCC).
- Gene deregulation occurs at various stages of bladder cancer development.
- Quantitative RT-PCR can assess ErbB pathway status for personalized therapy.
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