Lactation Gene Acts as Tumor Suppressor to Block Breast Cancer

Researchers have used a line of genetically engineered "knockout" mice to show that removal of a gene that normally regulates development of mammary glands stimulates the epithelial–mesenchymal transition (EMT) that characterizes formation of cancer cells.

Investigators at the University at Buffalo (NY, USA) and Princeton University (Princeton, NJ, USA) created a line of mice that lacked the gene for production of the transcription factor Elf5. As complete removal of the Elf5 gene was fatal for fetal development, these "conditional" knockout mice lacked the gene only in mammary tissue.

Results published in the October 21, 2012, online edition of the journal Nature Cell Biology revealed that in addition to malformations in tissues related to lactation, the genetically engineered animals showed increased EMT activity. Normally, Elf5 would suppress EMT by directly repressing the transcription of a protein known as Snail2, a master regulator of mammary stem cells and a known inducer of EMT.

"This is the first confirmed report that this protein, called Elf5, is a tumor suppressor in breast cancer," said contributing author Dr. Satrajit Sinha, associate professor of biochemistry at the University of Buffalo. "We found that when Elf5 levels are low or absent, epithelial cells become more like stem cells, morphing into mesenchymal cells, changing their shape and appearance, and migrating elsewhere in the body. This is how cancer spreads."

"It seems that loss of Elf5 is an initial event in the disease, so it could also be an important diagnostic tool," said Dr. Sinha. "We want to know, how early does the loss of Elf5 occur? Could we use loss of Elf5 as a reliable diagnostic tool? Our research shows that the EMT-Snail 2 pathway is a valuable one to target for early breast cancer intervention, possibly by designing something to recapture the repressive effect of Elf5 or a drug that could mimic Elf5 activity. And this is just one molecule, part of a big network. That's why we are now creating a detailed map of this molecule and its associated partners in order to give us a better idea of what to look for."

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