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Updated: Jun 4, 2026
Magnetic Resonance Imaging Assessment of Carcinogen-induced Murine Bladder Tumors
Published on: March 29, 2019
Expression of NRG1 and its receptors in human bladder cancer
J A Forster1, A B Paul, P Harnden
1Cancer Research UK Clinical Centre, St James University Hospital, Beckett Street, Leeds LS9 7TF, UK.
Background:
Therapies targeting ERBB2 have shown success in the clinic. However, response is not determined solely by expression of ERBB2. Levels of ERBB3, its preferred heterodimerisation partner and ERBB ligands may also have a role.
Methods:
We measured NRG1 expression by real-time quantitative RT-PCR and ERBB receptors by western blotting and immunohistochemistry in bladder tumours and cell lines.
Results:
NRG1α and NRG1β showed significant coordinate expression. NRG1β was upregulated in 78% of cell lines. In tumours, there was a greater range of expression with a trend towards increased NRG1α with higher stage and grade. Increased expression of ERBB proteins was detected in 15% (EGFR), 20% (ERBB2), 41% (ERBB3) and 0% (ERBB4) of cell lines. High EGFR expression was detected in 28% of tumours, associated with grade and stage (P=0.05; P=0.04). Moderate or high expression of ERBB2 was detected in 22% and was associated with stage (P=0.025). Cytoplasmic ERBB3 was associated with high tumour grade (P=0.01) and with ERBB2 positivity. In cell lines, NRG1β expression was significantly inversely related to ERBB3, but this was not confirmed in tumours.
Conclusion:
There is a wide spectrum of NRG1 and ERBB receptor expression in bladder cancer. In advanced tumours, EGFR, ERBB2 and ERBB3 upregulation is common and there is a relationship between expression of ERBB2 and ERBB3 but not the NRG1 ligand.
Insights
Bladder cancer treatment response depends on more than ERBB2. This study found varied expression of ERBB2, ERBB3, and NRG1 ligands in tumors, impacting treatment outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Targeted therapies for ERBB2-positive cancers show clinical success.
- Cancer treatment response is influenced by factors beyond ERBB2 expression, including ERBB3 and ERBB ligands.
- ERBB3 acts as a preferred heterodimerization partner for ERBB2.
Purpose of the Study:
- To investigate the expression patterns of Neuregulin 1 (NRG1) and ERBB receptors in bladder cancer.
- To determine the relationship between NRG1 ligands and ERBB receptor expression in bladder tumors and cell lines.
- To explore the clinical relevance of these molecular markers in bladder cancer progression.
Main Methods:
- Quantitative real-time RT-PCR was used to measure NRG1 expression.
- Western blotting and immunohistochemistry were employed to assess ERBB receptor expression (EGFR, ERBB2, ERBB3, ERBB4).
- Analyses were conducted on both bladder tumor tissues and established cell lines.
Main Results:
- NRG1α and NRG1β demonstrated coordinated expression, with NRG1β upregulated in 78% of cell lines.
- Tumor samples showed a broad range of NRG1α expression, trending higher with increased stage and grade.
- Upregulation of EGFR (28%), ERBB2 (22%), and ERBB3 (41%) was observed in tumors and cell lines, with associations to tumor stage, grade, and ERBB2 positivity.
Conclusions:
- Bladder cancer exhibits diverse expression levels of NRG1 and ERBB receptors.
- Advanced bladder tumors frequently display upregulation of EGFR, ERBB2, and ERBB3.
- A correlation exists between ERBB2 and ERBB3 expression, but not with the NRG1 ligand, in bladder tumors.
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