The research was presented at the 96th Annual Meeting of the American Association for Cancer Research (AACR) in Anaheim, Calif. BRCC36 directly interacts with the BRCA1 protein. Almost all invasive breast cancer cells have elevated BRCC36 levels compared to normal breast milk-duct cells.

"Since BRCC36 directly affects BRCA1 and BRCA1 is activated after exposure to radiation, we wanted to see if BRCC36 might be important in this response," said Xiaowei Chen, Ph.D., a Fox Chase postdoctoral researcher in the laboratory of geneticist Andrew K. Godwin, Ph.D., and the study's lead author.

Working with breast-cancer cell line MCF-7, the Fox Chase scientists reduced BRCC36 expression by 80 percent. They then exposed the cells to radiation, similar to that used in breast cancer treatment. They found that the number of breast cancer cells killed by the radiation increased by about 10 percent compared to cells that did not have their BRCC36 levels reduced.

"These findings hold promise for future breast cancer treatments," Chen said. "BRCC36 may be a target to manage radiation-resistant breast cancer cells. Our next step is to find out why the cells with reduced BRCC36 are more sensitive to radiation."

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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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