TY - JOUR
T1 - Identification of novel growth factor-responsive genes in neuroendocrine gastrointestinal tumour cells
AU - Hofsli, E
AU - Thommesen, L
AU - Yadetie, F
AU - Langaas, M
AU - Kusnierczyk, W
AU - Falkmer, U
AU - Sandvik, AK
AU - Laegreid, A
PY - 2005/4/25
Y1 - 2005/4/25
N2 - 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.
AB - 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.
KW - Carcinoid Tumor/genetics
KW - Cell Line, Tumor
KW - Cell Proliferation/drug effects
KW - Gene Expression Profiling
KW - Gene Expression Regulation/physiology
KW - Growth Substances/pharmacology
KW - Humans
KW - In Situ Hybridization
KW - Pancreatic Neoplasms/genetics
KW - Reverse Transcriptase Polymerase Chain Reaction
U2 - 10.1038/sj.bjc.6602535
DO - 10.1038/sj.bjc.6602535
M3 - Journal article
C2 - 15846300
SN - 0007-0920
VL - 92
SP - 1506
EP - 1516
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 8
ER -