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AKT2 Oncogene and Phosphoinositide 3-Kinase in Human Breast Cancer
Annual rept. 20 Aug 2001-19 Aug 2002
UNIVERSITY OF SOUTH FLORIDA TAMPA
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We have detected alterations of AKT2 and PI3K at kinase and protein levels in 32 of 80 human primary breast carcinomas. The majority of the cases with the kinase activation are ER positive and late stage and high grade tumors. We have also shown that ER-alpha interacts with p85 regulatory subunit of PI3K and activates P13KAKT2 pathway. Moreover, activated PI3K and AKT2 induce ER-alpha transcriptional activity by phosphorylation of Serine-167 of ER-alpha, suggesting that regulation between P13KAKT2 and ER-alpha plays a pivotal role in mammary oncogenesis and that activation of PI3KAKT2 contributes to ligand-independent breast cancer cell growth. In addition, we have demonstrated that AKT2 is activated by cellular stress and TNF-alpha in human epithelial cells The activated AKT2 inhibits both JNK and p38 stress kinase activation and protects cells from UV, Heat shock and TNF-alpha-induced apoptosis. AKT2-inhibited JNK1 activation is mediated by AKT2-induced NFkB.
APPROVED FOR PUBLIC RELEASE