Researchers find more clues to causes of breast cancer

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 ."

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.

Provided by H. Lee Moffitt Cancer Center & Research Institute

not rated yet
add to favorites email to friend print save as pdf

Related Stories

An Achilles heel in cancer cells

Dec 08, 2008

A protein that shields tumor cells from cell death and exerts resistance to chemotherapy has an Achilles heel, a vulnerability that can be exploited to target and kill the very tumor cells it usually protects, researchers ...

Recommended for you

US women's awareness of breast density varies

2 hours ago

Disparities in the level of awareness and knowledge of breast density exist among U.S. women, according to the results of a Mayo Clinic study published in the Journal of Clinical Oncology.

Study shows why some brain cancers resist treatment

2 hours ago

Scientists at The University of Texas MD Anderson Cancer Center may have discovered why some brain cancer patients develop resistance to standard treatments including radiation and the chemotherapy agent temozolomide.

Researchers identify genes responsible for lung tumors

4 hours ago

The lung transcription factor Nkx2-1 is an important gene regulating lung formation and normal respiratory functions after birth. Alterations in the expression of this transcription factor can lead to diseases such as lung ...

Lycopene may ward off kidney cancer in older women

6 hours ago

A higher intake by postmenopausal women of the natural antioxidant lycopene, found in foods like tomatoes, watermelon and papaya, may lower the risk of renal cell carcinoma, a type of kidney cancer.

User comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.