TAMPA, Fla. -- Publishing in the current issue of The Journal of Biological Chemistry (Vol. 286, No 43), researchers at Moffitt Cancer Center in Tampa, Fla., have discovered additional mechanisms of "Akt" activation and suggest a component of that activation mechanism – inhibitor of nuclear factor kappa-B kinase subunit epsilon (IKBKE) – could be targeted as a therapeutic intervention for treating cancer.
Akt, also known as protein kinase B, is one of about 500 protein kinases in the human genome. Kinases are known to regulate the majority of cellular pathways. Akt modifies other proteins chemically and regulates cell proliferation.
"Recent evidence suggests that IKBKE is an oncogenic kinase that participates in malignant transformation and tumor development," said Moffitt senior researcher and lead author Jin Q. Cheng, Ph.D., M.D. "Our study identified Akt as a bona fide substrate of IKBKE and IKBKE direct activation of Akt independent PI3K and revealed a functional link between IKBKE and Akt activation in breast cancer."
Cheng's lab studies a variety of genetic alterations and their molecular mechanisms in both ovarian and breast cancer, particularly on their effect on the molecules that are regulated by Akt and the small molecule inhibitors of Akt.
"We found that inhibition of Akt suppresses IKBKE's oncogenic transformation," said Cheng. "This is significant because overexpression of IKBKE and activation of Akt has been observed in more than 50 percent of human cancers. Akt inhibitors targeting PH domain do not have inhibitory effect on IKBKE-induced Akt."
The researchers experimented with a variety of inhibitors currently being used in clinical trials.
The laboratory study utilized breast cancer cell lines from received from patient donors at Moffitt and cell lines received from Harvard University and Johns Hopkins University. The work was supported by a National Institutes of Health grant and a grant from the James and Esther King Biomedical Research Program.
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Located in Tampa, Moffitt Cancer Center is Florida's only NCI Comprehensive Cancer Center, a designation that recognizes Moffitt's excellence in research and contributions to clinical trials, prevention and cancer control. Moffitt currently has 14 affiliates in Florida, one in Georgia, one in Pennsylvania and two in Puerto Rico. Additionally, Moffitt is a member of the National Comprehensive Cancer Network, a prestigious alliance of the country's leading cancer centers, and is listed in U.S. News & World Report as one of "America's Best Hospitals" for cancer. Moffitt marks a very important anniversary in 2011 - 25 years committed to one mission: to contribute to the prevention and cure of cancer.
Journal
Journal of Biological Chemistry