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Published on: July 22, 2020
Identification of novel growth factor-responsive genes in neuroendocrine gastrointestinal tumour cells
E Hofsli1, L Thommesen, F Yadetie
1Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Medisinsk Teknisk Forskningssenter, Trondheim N-7489, Norway. eva.hofsli@ntnu.no
Abstract:
Targeting growth-regulatory pathways is a promising approach in cancer treatment. A prerequisite to the development of such therapies is characterisation of tumour growth regulation in the particular tumour cell type of interest. In order to gain insight into molecular mechanisms underlying proliferative responses in neuroendocrine (NE) gastrointestinal (GI) tumours, we investigated gene expression in human carcinoid BON cells after exposure to gastrin, hepatocyte growth factor (HGF), pituitary adenylate cyclase-activating polypeptide or epidermal growth factor. We particularly focused on gastrin- and HGF-induced gene expression, and identified 95 gastrin- and 101 HGF-responsive genes. The majority of these genes are known mediators of processes central in tumour biology, and a number of them have been associated with poor prognosis and metastasis in cancer patients. Furthermore, we identified 12 genes that were regulated by all four factors, indicating that they may be universally regulated during NE GI tumour cell proliferation. Our findings provide useful hypotheses for further studies aimed to search for new therapeutic targets as well as tumour markers in NE GI tumours.
Insights
Researchers explored gene expression in neuroendocrine gastrointestinal tumors to understand growth regulation. They identified key genes influenced by growth factors, offering potential therapeutic targets and biomarkers for these cancers.
Area of Science:
- Oncology
- Molecular Biology
- Gastroenterology
Background:
- Targeting cancer growth pathways is crucial for effective treatment.
- Understanding tumor-specific growth regulation is essential for developing targeted therapies.
- Neuroendocrine (NE) gastrointestinal (GI) tumors require detailed molecular characterization.
Purpose of the Study:
- To investigate molecular mechanisms of proliferation in human carcinoid BON cells.
- To identify genes regulated by growth factors like gastrin and hepatocyte growth factor (HGF) in NE GI tumors.
- To uncover potential therapeutic targets and tumor markers for NE GI tumors.
Main Methods:
- Gene expression analysis in human carcinoid BON cells.
- Exposure of cells to gastrin, HGF, pituitary adenylate cyclase-activating polypeptide, and epidermal growth factor.
- Focus on differential gene expression induced by gastrin and HGF.
Main Results:
- Identified 95 gastrin-responsive and 101 HGF-responsive genes.
- Many identified genes are involved in central tumor biology processes.
- Discovered 12 genes commonly regulated by all four tested factors, suggesting universal regulation in NE GI tumor proliferation.
- Several identified genes are linked to poor prognosis and metastasis in cancer patients.
Conclusions:
- Gene expression profiling reveals key pathways in NE GI tumor proliferation.
- Identified gastrin- and HGF-responsive genes provide hypotheses for new therapeutic strategies.
- Commonly regulated genes may serve as universal markers for NE GI tumor growth.
- Findings support the search for novel therapeutic targets and biomarkers in NE GI tumors.