Predicting mechanism of biphasic growth factor action on tumor growth using a multi-species model with feedback control.

A large number of growth factors and drugs are known to act in a biphasic manner: at lower concentrations they cause increased division of target cells, whereas at higher concentrations the mitogenic effect is inhibited. Often, the molecular details of the mitogenic effect of the growth factor are known, whereas the inhibitory effect is not. Hepatoctyte Growth Factor, HGF, has recently been recognized as a strong mitogen that is present in the microenvironment of solid tumors.

A uniform human Wnt expression library reveals a shared secretory pathway and unique signaling activities.

Wnt ligands are secreted morphogens that control multiple developmental processes during embryogenesis and adult homeostasis. A diverse set of receptors and signals have been linked to individual Wnts, but the lack of tools for comparative analysis has limited the ability to determine which of these signals are general for the entire Wnt family, and which define subsets of differently acting ligands. We have created a versatile Gateway library of clones for all 19 human Wnts.

A role for YY1 in repression of dominant negative LEF-1 expression in colon cancer.

Lymphoid enhancer factor 1 (LEF-1) mediates Wnt signaling via recruitment of β-catenin to target genes. The LEF1 gene is aberrantly transcribed in colon cancers because promoter 1 (P1) is a Wnt target gene and is activated by TCF-β-catenin complexes. A second promoter in intron 2 (P2) produces dominant negative LEF-1 isoforms (dnLEF-1), but P2 is silent because it is repressed by an upstream distal repressor element.