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Scientists shut down pump action to break breast cancer cells' drug resistance
Date:9/28/2011

COLUMBUS, Ohio Breast cancer cells that mutate to resist drug treatment survive by establishing tiny pumps on their surface that reject the drugs as they penetrate the cell membrane making the cancer insensitive to chemotherapy drugs even after repeated use.

Researchers have found a new way to break that resistance and shut off the pumps by genetically altering those breast cancer cells to forcibly activate a heat-shock protein called Hsp27. This protein regulates several others, including the protein that sets up the pumps that turn away the chemotherapeutics.

In experiments, the common chemotherapy drug Doxorubicin killed about 50 percent more drug-resistant breast cancer cells in which Hsp27 had been activated than it did in normal drug-resistant cells.

Though these results have been shown only in cell cultures in a lab, they suggest that there someday could be a clinical way to use this approach to reverse the drug resistance that can develop in breast cancer cells. The study was conducted in MCF-7/adr breast cancer cells, which resist the effects of Doxorubicin.

"These cells are actually resistant to multiple drugs, so the resistance will be there even if clinicians move on to other chemotherapeutics. It's a serious issue," said Govindasamy Ilangovan, associate professor of internal medicine at Ohio State University and senior author of the research. "The plausible way to circumvent this effect is to suppress the resistance by shutting down the drug extrusion pump using molecular approaches. That is what we're trying to address."

The study appears in the Sept. 23 issue of the Journal of Biological Chemistry.

The researchers analyzed proteins in regular breast cancer cells from the MCF-7 cell line as well as multidrug resistant cells from the same line. The normal breast cancer cells are known to be sensitive to chemotherapy drugs.

The tests indicated that the normal cells contained HSF-1, the
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Contact: Govindasamy Ilangovan
govindasamy.ilangovan@osumc.edu
614-292-9064
Ohio State University
Source:Eurekalert

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