Figure 4

Context specific effects of HER-2 overexpression on the biological responses and transcription program induced by transforming growth factor (TGF)-β in breast cancer cells. (a) Phenotypes of the luminal MCF-7 and mesenchymal MDA-MB-231 cells with and without engineered HER-2 overexpression. The epithelial growth pattern of MCF-7 cells is characteristically altered by HER-2 overexpression, which promotes an elongated morphology and increased proliferation rates in vitro as well as faster growing tumor xenografts in vivo [12,13]. The MDA-MB-231 cells are heterogeneous with the majority of cells, having a spindle shaped morphology. The effect of HER-2 overexpression on the morphological appearance was not dramatic except that significantly more (approximately three times) of the large, flattened round cells were observed. The MDA-MB-231 H2 cells have also been shown to be more metastatic in vivo than the MDA-MB-231 CN or parental lines (data not shown). (b) Summary of the TGF-β transcriptional program obtained by Affymetrix microarray profiling of cells treated with recombinant TGF-β1. The number of elements significantly affected (p < 0.01 and fold change greater than ± 1.7 using Rosetta Resolver) are graphed. Light and dark red indicate genes upregulated after 6 h and 24 h, respectively, and light and dark green represent genes downregulated after 6 and 24 h, respectively. (c) Highlighted genes from the dominant functional gene signatures as determined by the gene ontology information found in Source [105] and GeneCards [106]. Red and green indicate TGF-β stimulated and repressed genes, respectively. ECM, extracellular matrix.