The results show that both adherent and re attached R2N1d cells developed research only tumors in 2 weeks with 1 107 cells. In contrast, the non adherent R2N1d cells in cell suspension did not form palpable tumors until 6 months post inoculation of the same number of cells. The tumor forming frequency of the non adherent cells was also lower Inhibitors,Modulators,Libraries compared with adherent and reattached cells, examined 6 months after subcuta neous injection of cells. All these newly formed tumors developed by the 3 types of cells expressed HER2 by immunohistochemical study. These results reaffirmed the important role of HER2 in tumor development. Discussion and Conclusions HER2 as an important breast cancer oncogene is well known from the frequent amplification or overexpres sion of this Inhibitors,Modulators,Libraries gene in aggressive breast tumors and the efficacy of anti HER2 antibody, Herceptin, in treat ment of breast cancer with HER2 overexpression.

Although some functions and mechanisms of HER2 in breast tumor development have been delineated, the exact mechanisms of action of this gene have not been completely understood. By comparison of phenotypic differences Inhibitors,Modulators,Libraries of two cell lines derived from a common breast epithelial Inhibitors,Modulators,Libraries stem cell with homogeneous cellular context but differing in HER2 expression under same cell culture condition, we believe the results of this study should reveal more convincing and unambiguous information in regard to its mechanism of function. The biological effects of HER2 The biological effects induced by HER2 as revealed by the phenotypic differences between R2N1d and R2d cells and from HER2 inhibitor study include 1) the morpholo gical change from contact sensitive R2d cell culture to contact insensitive R2N1d cells with increas ing cell separation and motility .

2) the devel opment of fast growing invasive tumors, in contrast to R2d cells which were non tumorigenic, and. 3) increased cell invasion ability from HER2 Inhibitors,Modulators,Libraries inhibi tor study. Unlike R2dE, the http://www.selleckchem.com/products/Sunitinib-Malate-(Sutent).html tumors developed by R2N1d cells did not require estrogen treatment and the resulting tumors were significantly larger. The aver age size of tumors developed by R2N1d cells is comparable to tumors formed by the parental M13SV1R2N1 cells which is 295 mg and 11. 2 mm in dia meter and much larger than tumors developed by R2dE cells. Other major phenotypes of R2d and R2N1d and their parental cell lines are summarized in Additional file 4, Table S2. Major effects of HER2 on gene expression The comparison of gene expression profiles between R2d and R2N1d cells by using the Human WG 6 Bead Chip reveals that many genes related to cell adhesion, migration, metastasis, inflammation and angiogenesis have been significantly activated.