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Used in a new way, RNA interference permanently silences key breast cancer gene

breast cancer. When hijacked by a cancer cell, the activated gene is believed to interfere with the ability of key immune cells to attack a growing tumor.

Investigators used the lentivirus to permanently insert the RNAi into the genome of the cancer cell. After a single exposure of this delivery system, they found 75 percent of laboratory breast cancer cells stopped expressing the STAT3 protein. The researchers also discovered that expression of a protein called TWIST that is known to be involved in cancer metastasis was drastically reduced in the STAT3 knockdown cells, thus greatly reducing the ability of these cancer cells to invade normal tissues like the lung. "Somehow STAT3 is controlling TWIST expression, and this is important to know with regards to activated STAT3 and its involvement in cancer metastasis," Arlinghaus says.

When the mouse breast cells transduced with STAT3, shRNA were then tested in immunocompetent mice, researchers found that the treated breast cancer cells were unable to form breast tumors either at the site of injection or at distant sites typically involved in metastatic breast cancer in this mouse model.

Arlinghaus points out that a human therapy based on these findings is not on the horizon because lentivirus delivery systems haven't been approved for human use yet, and because of the many problems associated with treating metastatic breast cancer. But he says that proof that RNAi can be used to permanently silence such critical genes as STAT3 "has potential application for treating breast cancer."


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


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