墨菲特研究中心发现更多诱发乳腺癌的因素

Publishing in the current issue of The Journal of Biological Chemistry, researchers at Moffitt Cancer Center in Tampa, Fla., have discovered additional mechanisms² of "Akt" activation³ and suggest a component⁴ of that activation mechanism¹ -- inhibitor of nuclear factor kappa-B kinase subunit epsilon (IKBKE) -- could be targeted as a therapeutic⁵ intervention⁶ for treating cancer. Akt, also known as protein kinase（蛋白激酶） B, is one of about 500 protein kinases in the human genome. Kinases are known to regulate the majority of cellular⁷ pathways. Akt modifies other proteins chemically and regulates cell proliferation.

"Recent evidence suggests that IKBKE is an oncogenic（致瘤的） kinase that participates in malignant⁸ transformation⁹ and tumor¹⁰ development," said Moffitt senior researcher and lead author Jin Q. Cheng, Ph.D., M.D. "Our study identified Akt as a bona fide（善意的，真实的） substrate of IKBKE and IKBKE direct activation of Akt independent PI3K and revealed a functional¹¹ link between IKBKE and Akt activation in breast cancer."

Cheng's lab studies a variety of genetic¹² alterations¹³ and their molecular¹⁴ mechanisms in both ovarian and breast cancer, particularly on their effect on the molecules¹⁶ that are regulated by Akt and the small molecule¹⁵ 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 domain¹⁷ do not have inhibitory（禁止的） effect on IKBKE-induced Akt."

The researchers experimented with a variety of inhibitors currently being used in clinical trials.

The laboratory study utilized¹⁸ breast cancer cell lines from received from patient donors¹⁹ 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.