Expression of endothelins and their receptors promotes an invasive phenotype of breast tumor cells but is insufficient to induce invasion in benign cells
2005 | journal article. A publication with affiliation to the University of Göttingen.
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Expression of endothelins and their receptors promotes an invasive phenotype of breast tumor cells but is insufficient to induce invasion in benign cells
Hagemann, T.; Binder, C.; Binder, L.; Pukrop, T.; Truemper, L. H. & Grimshaw, M. J. (2005)
DNA and Cell Biology, 24(11) pp. 766-776. DOI: https://doi.org/10.1089/dna.2005.24.766
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- Authors
- Hagemann, T.; Binder, Claudia; Binder, L.; Pukrop, Tobias; Truemper, Lorenz H.; Grimshaw, M. J.
- Abstract
- There is increased staining of endothelins (ET-1, - 2, and - 3) and receptors (ET-RA and - RB) in invasive breast tumors compared to nonneoplastic tissue, and ETs stimulate MCF-7 cell invasion in vitro. We analyzed ET-stimulation of benign and transformed mammary epithelial cells, and whether expression of ETs is sufficient to induce invasiveness. In breast cancer patient serum, ET-1 was increased in those patients with lymph node metastases compared to those with no lymph node involvement; ETs, however, had no mitogenic effect on breast tumor cell lines in vitro. The benign mammary epithelial cell line, hTERT-HME1, and the poorly invasive breast tumor cell line MCF-7 secreted low levels of ET-1, while the invasive cell lines SKBR3 and MDAMB231 secreted high levels. Expression of the ETs and receptors by the cell lines broadly correlated with their in vitro invasiveness; overexpression of ETs in MCF-7 cells increased basal invasion. ET-mediated invasion involved both receptors and a calcium influx to induce a pertussis toxin-sensitive MAPK pathway. MMP-14 activity was induced via ET-RA in an autocrine manner. In contrast to transformed cells, ET stimulation or overexpression did not induce an invasive phenotype in benign cells. Benign cells do not respond to ETs, and ET expression is not sufficient to induce invasion; however, the level of ET production by tumor cells correlates with their invasiveness, and increasing expression of the ET axis promotes breast tumor cell invasion via both receptors, while MMP-14 is induced via ET-RA.
- Issue Date
- 2005
- Status
- published
- Publisher
- Mary Ann Liebert Inc
- Journal
- DNA and Cell Biology
- ISSN
- 1044-5498