sell

compound libraries Once activated, Akt promotes cellular proliferation and inhibits apoptosis through phosphorylation of multiple substrates, includ ing caspase 9, Bad, GSK3, and forkhead transcription fac tors, such as FKHR, FKHRL, and AFX. Activation of PI3K Akt signaling is important in most human malignancies, including hematopoietic, melanoma, non small cell Inhibitors,Modulators,Libraries lung, pancreatic, endometrial and ovarian, breast, prostate, hepatocellular, and brain cancers. PTEN, the primary negative regulator of the PI3K Akt signaling pathway, is an important tumor suppressor. Deletions or inactivating mutations of PTEN are found in various cancer specimens, cancer cell lines, and inherited cancer predisposition syndromes, making PTEN one of the most commonly inactivated tumor sup pressor genes in human cancer.

Recently, muta tions in PIK3CA were observed in multiple cancers, including brain tumors, further supporting the fundamental role of PI3K pathway activation in the pathogenesis of human cancer. PTEN is among the most frequently mutated Inhibitors,Modulators,Libraries or deleted tumor suppressor genes in GBM, as genetic and epigenetic alterations have been identified in at least 60% of patients. Importantly, the role of PI3K Akt signaling in gliom agenesis has been demonstrated in both animal and cell culture models. Activating Akt by deletion of PTEN or by Myr Akt expression has been shown to increase tumor incidence, accelerate tumor onset, and Inhibitors,Modulators,Libraries elevate tumor malignancy in multiple mouse glioma models. Akt activation is also crucial for the transformation of human astrocytes in vitro, and EGFR, an upstream regulator of PI3K Akt signaling, is also commonly activated in GBM.

Activation of the PI3K Akt signaling pathway Inhibitors,Modulators,Libraries is associated with radioresistance in many cancers, including those of the colon, bladder, prostate, head and neck, cervix, and brain. Inhibition of the PI3K Akt pathway has been shown to impair DNA repair after IR, and result in radiosensitization in a variety of different cell types including human GBMs For example, inhi bition Inhibitors,Modulators,Libraries of PI3K Akt pathway selleck chemical via treatment with PI3K inhibitors or PTEN expression has been shown to increase radiosensitivity in human GBM cells. Although most reports indicate that inhibition of Akt activation reduces radiosensitivity, a report from del la Pena et al showed little or no effect of Akt activation on the effective ness of IR treatment in a number of human GBM cell lines. Importantly, IR has been shown to induce Akt activation in multiple cell types, including some human GBM cells. In this study, we investigated PI3K Akt activation following irradiation in multiple GBM cell lines, and assessed its effect on the ability of human gliobastoma cell lines to respond to IR treatment.

Leave a Reply

Your email address will not be published. Required fields are marked *

*

You may use these HTML tags and attributes: <a href="" title=""> <abbr title=""> <acronym title=""> <b> <blockquote cite=""> <cite> <code> <del datetime=""> <em> <i> <q cite=""> <strike> <strong>