Overabundance of protein promotes growth of breast cancer stem cells

February 16th, 2011 - 4:52 pm ICT by ANI  

Washington, Feb 16 (ANI): Scientists at The University of Texas MD Anderson Cancer Center have said that an essential protein for normal stem cell renewal also promotes the growth of breast cancer stem cells when it’s overproduced in those cells.

In mouse and lab experiments, the team also discovered that two drugs block the cascade of molecular events that they describe in the paper, thwarting formation of breast tumor initiating cells.

“Overexpression of the EZH2 protein has been linked to breast cancer progression, but the molecular details of that connection were unknown,” said senior author Mien-Chie Hung of the MD Anderson’s Department of Molecular and Cellular Oncology.

“Tumor-initiating cancer cells that arise from the primary cancer stem cells also are thought to drive cancer progression. This research connects EZH2 to the growth of breast tumor-initiating cells,” said Hung.

The molecular chain of events that improves self-renewal, survival and growth of these breast cancer stem cells can be initiated by oxygen-starved portions of a tumor, said Hung. This hypoxia stimulates a protein that in turn causes overexpression of EZH2.

The team showed that abundant EZH2, dampens production of an important protein involved in DNA damage repair.

The team tested five anti-cancer drugs against a culture of breast cancer cells and in tumor samples of human breast cancer in a mouse model. Sorafenib, a RAF inhibitor also known as Nexavar, eliminated more cancer stem cells and blocked tumor formation better than the other four.

Sorafenib inhibits multiple targets, so the researchers also tested an experimental drug called AZD6244, which specifically inhibits the MEK-ERK kinase cascade launched by RAF1. They found the drug eliminates EZH2-promoted breast cancer stem cells and blocks the formation of precancerous mammospheres.

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

The findings have been reported in the journal Cancer Cell. (ANI)

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