Abstract: MicroRNA (miRNA) profiling of cells showed unique miRNA signatures for each of three Akt isoforms. Among differentially regulated miRNA species, the miR-200 family was downregulated in Akt2-expressing cells. Akt1 knockdown inhibited expression of miR-200 and promoted TGF?-induced epithelial-mesenchymal-transition (EMT) and a stem cell like phenotype. Carcinomas developing in MMTV-cErb2/Akt1?/? mice exhibited increased invasiveness because of EMT induced by miR-200 downregulation. EMT was found to be controlled by miRNA species that are regulated by the balance between Akt1 and Akt2, rather than overall Akt levels.

Abstract: MicroRNA (miRNA) profiling of cells showed unique miRNA signatures for each of three Akt isoforms. Among differentially regulated miRNA species, the miR-200 family was downregulated in Akt2-expressing cells. Akt1 knockdown inhibited expression of miR-200 and promoted TGF?-induced epithelial-mesenchymal-transition (EMT) and a stem cell like phenotype. Carcinomas developing in MMTV-cErb2/Akt1?/? mice exhibited increased invasiveness because of EMT induced by miR-200 downregulation. EMT was found to be controlled by miRNA species that are regulated by the balance between Akt1 and Akt2, rather than overall Akt levels.

Abstract: An embodiment of the invention provides methods and compositions for immortalizing cells, and in another embodiment for reversing immortalization of cells. Methods for screening for anti-cancer agents by identifying compounds that bind to and inhibit activity of an Ndy protein are also provided. Novel cancer diagnostic and prognostic methods using Ndy1, Ezh2 and miR-101 are shown with samples of tissue or cell lines from cancers of lung, colon, ovary, bladder and transitional cell carcinoma.

Abstract: The present invention discloses novel methods to identify compounds potentially useful for the treatment and prevention of inflammation and/or cancer in animals including mammals. It disclose that Tpl2 is required for tumor induction by Akt and Tpl2 is required for the induction of cyclo-oxygenase-2 (COX-2) and prostaglandin synthesis and provides methods to identify compounds that modulate interactions between Tpl-2 and COX-2 or interactions between Tpl-2 and Akt. The present invention also discloses a transgenic Tpl2−/− mouse encoding Akt where the mouse is characterized by its ability to show delayed tumor induction by comparison with a transgenic Tpl2+/+ mouse expressing the Akt and method of treating cancers in animals.

Abstract: The present invention is directed to animal having functionally disrupted endogenous Tpl2. These animals are resistant to Lps induced endotoxin shock and TNF&agr;-mentioned inflammatory disease. A method of identifying Tpl2 specific inhibitors of endotoxin shock or antagonists to inflammation on and a method of treating or preventing TNF&agr;-mediated inflammatory diseases and Lps induced endotoxin shock in animals are also within the scope of this invention. The present invention is also directed to Tpl2 encoding nucleic acid molecules (SEQ ID NOS: 1 and 3) and polypeptides (SEQ ID NOS: 2 and 4) encoded by such molecules.

Abstract: Nucleic acid molecules, proteins and antibodies are provided which may be used in biological screens to identify therapeutic agents involved in the regulation of cell cycle progression and apoptotic cell death.

Abstract: The present invention discloses methods of modulating phosphoinositide 3-kinase (PI3K) activity or phosphatidylinositol-3,4,5-P3 (PIP3) production by targeting GTPase responsive domain or by expressing a p85 inhibitory domain of p85 subunit of phosphoinositide 3-kinase (PI3K) in cells. Methods for selecting modulators of PIP3 induction by small GTPases are also disclosed.