Egr-1 induction provides a genetic response to food aversion in zebrafish.

As soon as zebrafish larvae start eating, they exhibit a marked aversion for bitter and acidic substances, as revealed by a consumption assay, in which fluorescent Tetrahymena serve as a feeding basis, to which various stimuli can be added. Bitter and acidic substances elicited an increase in mRNA accumulation of the immediate-early response gene egr-1, as revealed by in situ hybridization. Conversely, chemostimulants that did not induce aversion did not induce egr-1 response.

E1A oncogene expression inhibits PTHrP P3 promoter activity and sensitizes human prostate cancer cells to TNF-induced apoptosis.

In the advanced stages of prostate cancer, tumor cells can evolve to become androgen-independent and resistant to injury-induced apoptosis. Tumor cell expression of parathyroid hormone-related protein (PTHrP) may contribute to the apoptosis phenotype. Expression of the adenovirus E1A oncogene repressed PTHrP promoter and mRNA expression in human PC-3 prostate cancer cells and increased the caspase 3 activation and sensitivity of these cells to apoptosis triggered by tumor necrosis factor alpha.

Preclinical anticancer activity of the potent, oral Src inhibitor AZD0530.

AZD0530, an orally available Src inhibitor, demonstrated potent antimigratory and anti-invasive effects in vitro, and inhibited metastasis in a murine model of bladder cancer. Antiproliferative activity of AZD0530 in vitro varied between cell lines (IC(50) 0.2 ->10μM).

Serine phosphorylation regulates paxillin turnover during cell migration.

Background: Paxillin acts as an adaptor protein that localizes to focal adhesion. This protein is regulated during cell migration by phosphorylation on tyrosine, serine and threonine residues. Most of these phosphorylations have been implicated in the regulation of different steps of cell migration.

Activation of Rac1 by paxillin-Crk-DOCK180 signaling complex is antagonized by Rap1 in migrating NBT-II cells.

Induction of epithelial cell motility is a fundamental morphogenetic event that is recapitulated during carcinoma metastasis. Random motility of NBT-II carcinoma cells on collagen critically depends on paxillin phosphorylation at Tyr-31 and Tyr-118, the binding sites for the adapter protein CrkII. Two constitutive partners of CrkII are the exchange factors DOCK180 and C3G.

Ras induces NBT-II epithelial cell scattering through the coordinate activities of Rac and MAPK pathways.

Cell dissociation and cell migration are the two main components of epithelium-mesenchyme transitions (EMT). We previously demonstrated that Ras is required for the accomplishment of both of these processes during the EGF-induced EMT of the NBT-II rat carcinoma cell line in vitro. In this study, we examined the downstream targets of Ras that are responsible for the dissociation and motility of NBT-II cells.

Src kinase contributes to the metastatic spread of carcinoma cells.

The involvement of Src kinase during carcinoma metastasis has been explored by using the NBT-II rat carcinoma cell line, which can be induced to scatter in vitro through Src activity. Here we show that Src activity was not required for growth of tumors derived from NBT-II cells injected into nude mice. In contrast, the presence of micrometastases was strictly dependent on Src, since the percentage of mice bearing metastases was dramatically reduced by the expression of a dominant-negative mutant of Src (SrcK-) or of Csk, the natural inhibitor of Src.