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Mechanisms of endothelin 1-stimulated proliferation in colorectal cancer cell lines.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Grant, K. Knowles, Joseph A. Dawas, Khaled I. Burnstock, Geoffrey Taylor, Irving Loizidou, Marilena |
| Copyright Year | 2007 |
| Abstract | BACKGROUND The peptide endothelin (ET) 1 promotes proliferation in a number of epithelial cancers. The aim of this study was to identify the mechanism of ET-1-stimulated proliferation in colorectal cancer cells in vitro. METHODS The effects of ET-1 on colorectal cancer cell lines HT29, LIM1215 and SW620 were studied. Cells were cultured with ET-1 plus antagonists/inhibitors to ET(A) or ET(B) receptors, G protein subtypes, phosphoinositide 3-kinase (PI3K) or protein kinase C (PKC). DNA replication and apoptosis were investigated by 5-bromo-2'-deoxyuridine incorporation and Annexin V staining. Transactivation of the epidermal growth factor (EGF) receptor was investigated by blockade of the receptor in the presence of ET-1, measurement of levels of phosphorylated EGF receptor in the presence of ET-1, and comparing the effects of ET-1 and EGF on cell proliferation. RESULTS ET-1 significantly stimulated growth of all cell lines via ET(A) receptors. ET-1 stimulated DNA replication, not apoptosis. ET-1-stimulated growth was inhibited by antagonism of pertussis toxin-sensitive G proteins, PI3K and PKC. Inhibition of the EGF receptor reduced the effect of ET-1. ET-1 increased levels of phosphorylated EGF receptor via the ET(A) receptor. CONCLUSION ET-1 increased DNA replication in colorectal cancer cells via the ET(A) receptor. This mitogenic action was mediated via pertussis toxin-sensitive G proteins, PI3K, PKC and transactivation of the EGF receptor. |
| Starting Page | 1 |
| Ending Page | 4 |
| Page Count | 4 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.ucl.ac.uk/ani/GB's%20PDF%20file%20copies/CV1347.pdf |
| PubMed reference number | 17078114v1 |
| Volume Number | 94 |
| Issue Number | 1 |
| Journal | The British journal of surgery |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | 1-Phosphatidylinositol 3-Kinase 1-Phosphatidylinositol-4,5-bisphosphate phosphodiesterase Annexins Apoptosis Bromodeoxyuridine Cell Proliferation Colorectal Carcinoma Cultured Cell Line DNA Replication EGFR protein, human Endothelin Endothelin-1 Growth Factor HT29 Cells Malignant Neoplasms Non-Small Cell Lung Carcinoma Pertussis Toxin Phosphatidylinositols Protein Kinase C Protein Kinases Staining method Subtype (attribute) Trans-Activation, Genetic cancer cell |
| Content Type | Text |
| Resource Type | Article |
