William C. Hahn and his research team from the Broad Institute, which is associated with Harvard University and Massachusetts Institute of Technology, and Brigham and Women’s Hospital (BWH) recently discovered the I-kappa-B kinase epsilon (IKBKE) gene. They found that it is inappropriately being produced in about one-third of all women with breast cancer. As a comparison, most gene mutations appear in less than one percent of all breast cancer patients.

IKBKE is a muted gene that becomes overproduced, causing a stimulation production of cells. Their results appear in the June 15, 2007 issue of the journal Cell.

Unlike other genes, the IKBKE gene occurs during a woman’ life and is not inherited. Consequently, it is rare for it to cause breast cancer in women in early years of their lives. 

Hahn’s team used three established and complimentary approaches in a unique step-wise manner that allows the identification of many different genes using an advanced technology screening process.

The team first injected hundreds enzymes into normal, cultured breast cells—cell protein called Ras—in order to find which ones would develop abnormalities in cancer cells (both in Ras and its partner proteins, called kinases). Only five enzymes actually developed into cancer. Second, the group analyzed the genes that comprised these five enzymes to determine if they were present in cells taken from tumors of breast cancer patients.

Only the IKBKE gene showed increased activity. Hahn’s group studied tumors from another group of breast cancer patients. They found that the enzyme produced by IKBKE occurred in about 30-40% of the samples.

In the third step, the research team used a technique called RNA (ribonucleic acid) interference to block the IKBKE gene. When the gene was isolated, it died. This activity showed to Hahn’s team that the cancerous cells were dependent on IKBKE.

The result of the Hahn study is considered an important step in breast cancer research for new treatments and a possible cure. The procedure by which the research was undertaken is also considered a breakthrough in genome research—allowing for the search of large numbers of genes through the use of advanced screening technology to find potential cancer-causing genes.

Future research will attempt to understand more specifics with the IKBKE gene and its association with breast cancer. Eventually, a drug to target IKBKE may be possible.

Dr. William C. Hahn is associated with the Department of Medicine, Dana-Farber Cancer Institute, Department of Medical Oncology. Lead authors of the study include Jesse Boehm, of Dana-Farber and the Broad Institute; Jean Zhao, of Dana-Farber and BWH; and Jun Yao, of Dana-Farber. Other senior authors include Thomas Roberts, of Dana-Farber; Kornelia Polyak, of Dana-Farber and Brigham and Women's Hospital; and Eric Lander, of the Broad Institute.

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