Stat3 mediates expression of autotaxin in breast cancer.

We determined that signal transducer and activator of transcription 3 (Stat3) is tyrosine phosphorylated in 37% of primary breast tumors and 63% of paired metastatic axillary lymph nodes. Examination of the distribution of tyrosine phosphorylated (pStat3) in primary tumors revealed heterogenous expression within the tumor with the highest levels found in cells on the edge of tumors with relatively lower levels in the central portion of tumors. In order to determine Stat3 target genes that may be involved in migration and metastasis, we identified those genes that were differentially expressed in primary breast cancer samples as a function of pStat3 levels.

Constitutively activated Stat3 induces tumorigenesis and enhances cell motility of prostate epithelial cells through integrin beta 6.

The persistent activation of signal transducer and activator of transcription 3 (Stat3) is a common feature of prostate cancer. However, little is known about the Stat3 targets that may mediate prostate tumorigenesis. The introduction of an activating mutant form of Stat3 (Stat3-C) into immortalized prostate epithelial cells resulted in tumorigenesis.

Pyridone 6, a pan-Janus-activated kinase inhibitor, induces growth inhibition of multiple myeloma cells.

Interleukin-6 (IL-6) and the subsequent Janus-activated kinase (JAK)-dependent signaling pathways play a critical role in the pathogenesis of multiple myeloma. Here, we compared the sensitivity and specificity of a novel pan-JAK inhibitor, tetracyclic pyridone 6 (P6), with that of AG490 in a panel of myeloma-derived cell lines. P6 induced growth arrest and subsequent apoptosis of the IL-6-dependent hybridoma and myeloma-derived cell lines (B9 and INA-6) grown either in IL-6-containing medium or in the presence of bone marrow-derived stromal cells (BMSC) using much lower concentrations of drug and with significantly faster kinetics than AG490.

Cyclin D1 is transcriptionally regulated by and required for transformation by activated signal transducer and activator of transcription 3.

Signal transducers and activators of transcription 3 (STAT3) is a transcription factor that is aberrantly activated in many cancer cells. Constitutively activated STAT3 is oncogenic, presumably as a consequence of the genes that it differentially regulates. Activated STAT3 correlated with elevated cyclin D1 protein in primary breast tumors and breast cancer-derived cell lines.

Redundancy of biological regulation as the basis of emergence of multidrug resistance.

Active efflux of xenobiotics is a major mechanism of cell adaptation to environmental stress. The ATP-dependent transmembrane transporter P-glycoprotein (Pgp) confers long-term cell survival in the presence of different toxins, including anticancer drugs (this concept is referred to as multidrug resistance, or MDR). The vital importance of this mechanism for cell survival dictates the reliability and promptness of its acquisition.

Selective susceptibility of transformed T lymphocytes to induction of apoptosis by PSC 833, an inhibitor of P-glycoprotein.

P-glycoprotein is a cellular efflux pump. The P-glycoprotein inhibitor PSC 833 causes apoptosis of cancer cells and induces a rise in the intracellular levels of ceramide. Our aims were to determine whether a cause and effect relationship exists between these two actions of PSC 833, and to assess whether the PSC 833-induced apoptosis is restricted to transformed cells.

Aspirin enhances multidrug resistance gene 1 expression in human Molt-4 T lymphoma cells.

Background: We recently found that aspirin induces the expression of P-glycoprotein (P-gp), a protein mediating drug resistance, in human prostate cancer cells. The purpose of this study was to evaluate the effect of aspirin on the expression of P-gp in a different human cancer type, i.e.

Overexpression of peptide-methionine sulfoxide reductase in Saccharomyces cerevisiae and human T cells provides them with high resistance to oxidative stress.

The yeast peptide-methionine sulfoxide reductase (MsrA) was overexpressed in a Saccharomyces cerevisiae null mutant of msrA by using a high-copy plasmid harboring the msrA gene and its promoter. The resulting strain had about 25-fold higher MsrA activity than its parent strain. When exposed to either hydrogen peroxide, paraquat, or 2,2'-azobis-(2-amidinopropane) dihydrochloride treatment, the MsrA overexpressed strain grew better, had lower free and protein-bound methionine sulfoxide and had a better survival rate under these conditions than did the msrA mutant and its parent strain.