The suppression of p70S6K with RPS6KB1 siRNAs did not induce apoptosis. Genes responsive to both PI3K mTOR pathway and p70S6K inhibitions selleck products reveal novel putative downstream targets of PI3K mTOR p70S6K pathway We also compared the individual gene expression profiles between Ly294002 and rapamycin treated and RPS6KB1 suppressed BT 474 and MCF 7 breast cancer cell lines to identify genes downstream of PI3K mTOR p70S6K path way. Expression of Inhibitors,Modulators,Libraries 17 genes was altered in BT 474 and MCF 7 breast cancer cell lines in response to both PI3K or mTOR inhibition and p70S6K inhibition with at least two siRNAs. In BT 474 cell line, these included 9 genes, e. g. ARL11 and CDKN2B. Also in MCF 7 cell line, 9 genes were differentially expressed after siRNA and inhib itor treatments including VTCN1, SCD and RELB.

ST3GAL6 was differentially expressed in both cell lines. Altogether, the inhibition of PI3K and mTOR in BT 474 and MCF 7 cells by Ly294002 and rapamycin led to differ ential expression of a higher number of genes than with novel drugs with high positive connectivity with our Ly294002 and rapamycin treated gene expression pro files included wortmannin, trichostatin Inhibitors,Modulators,Libraries A, and rottlerin. Discussion The 17q23 region is one of the most highly amplified regions in breast cancer and RPS6KB1 is considered one of its target genes. Due to RPS6KB1 amplification and overexpression in breast cancer and the role of p70S6K as a downstream mediator of PI3K mTOR pathway, our aim Protein level Ly294002 treated rapamycin treated RPS6KB1 siRNAs.

The number of differentially expressed genes Inhibitors,Modulators,Libraries after Ly294002 treatment was 530, whereas after Inhibitors,Modulators,Libraries rapamycin treatment it was 117. The higher number of genes after Ly294002 treatment is somewhat expected since Ly294002 inhibition caused the most effective biological response. Knock down of p70S6K caused differential expression of only 68 genes and no apoptosis was detected in BT 474 and MCF 7 cell lines. Gene ontology analysis and Connectivity Map support the known effects of Ly294002 and rapamycin as well as suggest new inhibitors with similar mechanism of action We then explored which gene ontology classes were enriched in gene expression profiles of five Ly294002 and rapamycin treated breast cancer cell lines by using Gene Ontology Categorizer. Among the twenty relatively most enriched GO classes in Ly294002 treated cell lines were functional Inhibitors,Modulators,Libraries categories involved in cell killing, mitosis, and G1 phase of the cell cycle.

In rapamycin treatment, these included functional categories such as mitosis, M phase of mitotic cell cycle and translational elongation. To identify other clinically approved drugs with potentially similar Rucaparib solubility mechanisms of action, we took advantage of the recently published Con nectivity Map, where connections of chemical or bio logical perturbations can be identified using a web based interface. As expected, Ly294002 gave the highest positive connectivity for Ly294002 treated samples.