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This activation was dependent on a Stat3 recognition element present at nt-95. The exception was the ErbB2 over-expressing cell line SK-BR-3 where Stat3 alone could transactivate HGF though Src augmented this effect. Increased phosphorylation of Stat3 tyrosine 705 was also observed in this line. Analysis of three ovarian cell lines revealed that Src\/Stat3 expression was not able to activate the HGF promoter in two of these lines (SKOV3 and IOSE-80PC). Src\/Stat3 expression did activate HGF transcription in OVCAR3 cells, but this effect was not mediated by the Stat3 site at nt-95. Stat3 phosphorylation at tyrosine 705 was observed in IOSE-80PC cells, but was insufficient to allow for activation of the HGF promoter. Human kidney (HEK293) and cervical carcinoma (HeLa) cells were also not Src\/Stat3 permissive, despite high levels of Stat3 phospho-Y705. These results suggest that human breast cells are a uniquely permissive environment for HGF transactivation by Src\/Stat3 which may allow for the inappropriate activation of HGF transcription during the early stages of breast transformation. This could lead to paracrine or autocrine activation of the Met receptor in breast carcinoma cells.<\/jats:p>","DOI":"10.1186\/1476-4598-6-69","type":"journal-article","created":{"date-parts":[[2007,10,30]],"date-time":"2007-10-30T05:40:49Z","timestamp":1193722849000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["A novel activating role of SRC and STAT3 on HGF transcription in human breast cancer cells"],"prefix":"10.1186","volume":"6","author":[{"given":"Michelle R","family":"Sam","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruce E","family":"Elliott","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher R","family":"Mueller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2007,10,29]]},"reference":[{"key":"277_CR1","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1002\/ijc.21808","volume":"119","author":"K Matsumoto","year":"2006","unstructured":"Matsumoto K, Nakamura T: Hepatocyte growth factor and the Met system as a mediator of tumor-stromal interactions. 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