The aim of the present study was to investigate the effect of short hairpin (sh)RNA targeting AKT1 and phosphatidylinositol 3-kinase (PI3K)/p85 on the proliferation and self-renewal of lung cancer stem cells (LCSCs). The recombinant adenovirus expression vector, which contained shRNA targeting open reading frames of AKT1 and PI3K/p85, was transfected into LCSCs. It was found that AKT1 and PI3K/...

The bioavailability of curcumin is the limiting factor for its effective use in anti-cancer therapy. Recently, we reported a novel approach to enhance the cellular uptake by conjugating curcumin with triphenyl phosphonium, named mitocurcumin-1. We found that such conjugation significantly increased the uptake of curcumin in various cancer cells and caused cancer cell death by inducing apoptosis...

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder associated mainly with tumors of multiple endocrine organs. Mutations in the MEN1 gene that encodes for the menin protein are the predominant cause for hereditary MEN1 syndrome. Though menin is a tumor suppressor, its molecular mechanism of action has not been defined. Here, we report that menin interacts with AKT1 in ...

To investigate molecular mechanisms involved in the development of cardiac hypertrophy and heart failure, we developed a tetracycline-regulated transgenic system to conditionally switch a constitutively active form of the Akt1 protein kinase on or off in the adult heart. Short-term activation (2 wk) of Akt1 resulted in completely reversible hypertrophy with maintained contractility. In contrast...

Skeletal integrity is dependent on the coordinated actions of bone-forming osteoblasts and bone-resorbing osteoclasts, which recognize and respond to multiple environmental inputs. Here we have studied the roles in bone development and growth of Akt1 and Akt2, two closely related signaling proteins, by evaluating mice lacking either of these enzymes. Global deficiency of Akt1 but not Akt2 cause...

Glucose homeostasis is controlled by insulin in part through the translocation of intracellular glucose transporter 4 to the plasma membrane in muscle and fat cells. Akt/protein kinase B downstream of phosphatidylinositol 3-kinase has been implicated in this insulin-signaling pathway, but results with a variety of reagents including Akt1-/- and Akt2-/- mice have been equivocal. Here we report t...

AKT-glycogen synthase kinase 3beta (GSK3beta) signaling is a target of lithium and has been implicated in the pathogenesis of mood disorders and schizophrenia. AKT1 protein level is decreased in the peripheral lymphocytes and brains of schizophrenic patients. The SNP2/3/4 TCG haplotype of AKT1 was associated with schizophrenia in patients with Northern European origin. In the present study, we ...

BACKGROUND The epidermal growth factor receptor (EGFR) signaling pathway is important in regulating biological behaviors in many malignancies. We explored whether expression and activation of EGFR and several components on its downstream pathways have prognostic significance in patients with esophageal squamous cell carcinoma (ESCC). METHODS Expression of EGFR, phosphorylated (p)-EGFR, AKT1, ...

Akt phosphorylation has previously been described to be involved in mediating DNA damage repair through the nonhomologous end-joining (NHEJ) repair pathway. Yet the mechanism how Akt stimulates DNA-protein kinase catalytic subunit (DNA-PKcs)-dependent DNA double-strand break (DNA-DSB) repair has not been described so far. In the present study, we investigated the mechanism by which Akt can inte...