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

In laboratory mouse experiments, researchers at The University of Texas M. D. Anderson Cancer Center have developed a way to use RNA interference (RNAi) so that it permanently hampers breast cancer development. The technique permanently silences activated STAT3, a crucial gene found in some human breast tumors, thus reducing the cancer's ability to become invasive.

The study, presented at the annual meeting of the American Association for Cancer Research (AACR), used a modified form of RNAi to silence STAT3 in a permanent way. Typically, only a transient effect is achieved with RNAi before the tiny bits of genetic material are become inactive as the cell population continues to expand.

"We are a long way from using this technique in patients, but this study shows that that it may be possible to use RNAi in more than just experiments that silence genes temporarily," says the study's principal investigator, Ralph Arlinghaus, Ph.D., a professor and chair of the Department of Molecular Pathology. Details of the study appeared in the April 1 2005 issue of the journal Cancer Research.

"The technique is also providing some valuable insights into the role of STAT3 and its downstream targets," adds Arlinghaus, who also will discuss the work in a mini symposium at the AACR meeting.

RNAi has been employed as a laboratory tool to knock down expression of genes in a variety of cells and organisms. It works by introducing a small double-stranded RNA (RNAi) that specifically targets a gene's product, its messenger RNA. This action then blocks translation and production of the protein that the gene encodes.

In this study, the researchers used a lentivirus (a type of retrovirus) to deliver a specifically designed long-acting small interfering RNA (termed a short hairpin RNA, shRNA) for mouse STAT3 into a mouse breast cancer cell line. They chose STAT3 because when activated, it is involved in the formation of multiple types of tumors, including
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Source:University of Texas M. D. Anderson Cancer Center


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