| Autor: |
Wojcik, E. J., Sharifpoor, S., Miller, N. A., Wright, T. G., Watering, R., Tremblay, E. A., Swan, K., Mueller, C. R., Elliott, B. E. |
| Předmět: |
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| Zdroj: |
Oncogene; 5/4/2006, Vol. 25 Issue 19, p2773-2784, 12p, 2 Charts, 7 Graphs |
| Abstrakt: |
In the normal breast, hepatocyte growth factor (HGF) is primarily expressed by stromal cells, and stimulates in a paracrine manner epithelial cells expressing the HGF receptor (Met). In invasive human breast carcinomas, HGF and Met are frequently overexpressed, possibly establishing an autocrine HGF/Met loop that promotes tumour cell invasion. However, the mechanisms leading to autocrine HGF expression in carcinoma cells are not known. We previously demonstrated a cooperative effect between c-Src and Stat3 in the activation of HGF transcription in mammary carcinoma cells. The present report defines a novel Stat3 consensus site at nt −95 in the HGF promoter that is highly conserved in human and mouse, and is required for c-Src and Stat3 to activate HGF transcription in breast epithelial cells. DNA–protein binding studies demonstrated high affinity binding of a Stat3-containing complex to the nt −95 site. Endogenous Stat3 binding to this region of the HGF promoter in carcinoma cells expressing HGF was demonstrated using a chromatin immunoprecipitation assay. In addition, coexpression of Stat3 and activated c-Src caused increased expression of endogenous HGF mRNA and protein and marked cell scattering in breast epithelial cells. Our results delineate a novel c-Src/Stat3-dependent mechanism that regulates HGF promoter activity, and is linked to transformation of mammary epithelial cells.Oncogene (2006) 25, 2773–2784. doi:10.1038/sj.onc.1209306; published online 9 January 2006 [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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