Molecular dissection of Pax6 function: the specific roles of the paired domain and homeodomain in brain development.

The transcription factor Pax6 plays a key role during development of various organs, including the brain where it affects cell fate, cell proliferation and patterning. To understand how Pax6 coordinates these diverse effects at the molecular level, we examined the role of distinct DNA-binding domains of Pax6, the homeodomain (HD), the paired domain (PD) and its splice variant (5a), using loss- and gain-of-function approaches. Here we show that the PD is necessary for the regulation of neurogenesis, cell proliferation and patterning effects of Pax6, since these aspects are severely affected in the developing forebrain of the Pax6Aey18 mice with a deletion in the PD but intact homeo- and transactivation domains.

Transforming growth factor beta regulates cell-cell adhesion through extracellular matrix remodeling and activation of focal adhesion kinase in human colon carcinoma Moser cells.

Transforming growth factor (TGF) beta is a potent regulator of cell-matrix and cell-cell adhesions (collectively termed cellular adhesions). Cellular adhesions play crucial roles in controlling the differentiation of epithelial cells and in maintaining the integrity of the epithelium. Loss of TGF beta-responsiveness is thought to be an important early initiating event in the malignant progression of epithelial cancer.

Extracellular calcium and calcium sensing receptor function in human colon carcinomas: promotion of E-cadherin expression and suppression of beta-catenin/TCF activation.

Ca(2+) has chemopreventive activity against colon cancer, albeit its mechanisms of action are not understood. In this study, we showed that four different human colon carcinoma cell lines (FET, SW480, MOSER, and CBS) expressed the human parathyroid calcium sensing receptor (CaSR) and that a function of extracellular Ca(2+) and the CaSR in these cells was the promotion of E-cadherin expression and suppression of beta-catenin/T cell factor activation. We also found that human colonic crypt epithelial cells expressed the CaSR, and histologically differentiated carcinomas (i.

Antioxidant response element-mediated 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induction of human NAD(P)H:quinone oxidoreductase 1 gene expression.

Antioxidant response element (ARE) is required for high basal expression of the human NAD(P)H:quinone oxidoreductase 1 (NQO1) gene in tumor cells and its induction in response to beta-naphthoflavone and phenolic antioxidants. In this study, we have demonstrated that ARE also is required for induction of human NQO1 gene expression in response to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The various results suggest an alternate pathway for TCDD induction of human NQO1 gene expression.