Protein Expands Breast Cancer Stem Cells

Posted by Admin on February 7, 2011
A new study from researchers at The University of Texas MD Anderson Cancer Center that was published in Cancer Cell, reports that an essential protein for normal stem cell renewal which promotes the growth of breast cancer stem cells when it's overproduced.

According to the head author of the study, Mien-Chie Hung, Ph.D., professor and chair of MD Anderson's Department of Molecular and Cellular Oncology, "Over-expression of the EZH2 protein has been linked to breast cancer progression, but the molecular details of that connection were unknown…this research connects EZH2 to the growth of breast tumor-initiating cells."  The chain of events that improves the self-renewal, survival, and growth of breast cancer stem cells can be started by the oxygen-starved portions of a tumor, which in turn stimulates a protein that causes an over-expression of EZH2.

In addition, the team also discovered that two separate drugs stop the chain of molecular events, thereby stopping the creation of breast tumor-initiating cells. The researchers tested five anti-cancer drugs against a culture of breast cancer cells in tumor samples of human breast cancer in a mouse model. One of the drugs, Sorafenib, a RAF inhibitor, eliminated more cancer stems cells and blocked tumor formation. Because Sorafenib inhibits multiple targets, so the researchers also tested a drug in the experimental stage called AZD6224, which specifically inhibits the MEK-ERK cascade launched by RAF1. The researchers discovered that this drug eliminated the EZH2-promoted breast cancer stem cells and blocked the formation of precancerous mammospheres.

According to Dr. Hung, "The drugs' inhibition of the breast tumor-initiating cells reveals a previously unidentified therapeutic effect for RAF1-ERK inhibitors to prevent breast cancer progression…AZD6244 is being tested in multiple clinical trials, and it will be interesting to see whether the cancer-stem-cell-killing ability will be induced in those trials.”

Source: University of Texas M. D. Anderson Cancer Center

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