Fig. 3.

Early and late mouse TGF-β gene expression signatures discriminate two subtypes of human HCC-derived cell lines with distinct invasiveness behaviors. (A) Dendrogram and heat-map overview of early and late mouse TGF-β signatures integrated with the gene expression profiles of 19 human HCC-derived cell lines. Clustering was based on the expression of 249 orthologous genes and the data are presented in a matrix format in which rows and columns represent genes and samples, respectively. Cell lines that cluster with mouse samples corresponding to WT hepato-cytes challenged with TGF-β for 0.5 to 2 hours (early signature) or for 4 to 24 hours (late signature) are colored in blue and red, respectively. (B) Early and late TGF-β signatures predict invasiveness of HCC-derived cell lines. Invasive and migrating activity of HCC cell lines was measured by using the BD BioCoat Matrigel Invasion Chambers as described in Materials and Methods. Invasion and migration of HCC cell lines defined by the late TGF-β signature (black column) were higher than those defined by the early TGF-β signature (white column). Columns, mean; bars, standard error of the mean (SEM), n = 3.