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September 20, 2005

Genetic Research Uncovers New Breast Cancer Target

Topics: Medicine

US researchers report that a genetic pathway linked to breast cancer recurrence may prove to be a new target for treatment. The pathway was identified in research with mice and substantiated in laboratory tests of human breast cancer samples. The findings appear in the September issue of the journal Cancer Cell.

Breast cancer recurrence is a fundamental clinical manifestation of tumor progression and represents the principal cause of death from this disease. Using a conditional transgenic mouse model for the recurrence of HER2/neu-induced mammary tumors, we demonstrate that the transcriptional repressor Snail is spontaneously upregulated in recurrent tumors in vivo and that recurrence is accompanied by epithelial-to-mesenchymal transition (EMT). Consistent with a causal role for Snail in these processes, we show that Snail is sufficient to induce EMT in primary tumor cells, that Snail is sufficient to promote mammary tumor recurrence in vivo, and that high levels of Snail predict decreased relapse-free survival in women with breast cancer. In aggregate, our observations strongly implicate Snail in the process of breast cancer recurrence.
The researchers found that, in mice, recurrent mammary tumors displayed characteristics of cellular changes previously linked with breast cancer. The tumors also had increased levels of a transcriptional repressor - a gene that affects the activity of other genes -- called "Snail."

The study found that levels of Snail were sufficient to induce the cellular changes in primary breast cancer cells and to promote mammary tumor recurrence in mice. When the researchers screened human breast cancer samples, they found that high levels of Snail expression also strongly predicted relapse in breast cancer patients.

The study's leader Dr. Lewis A. Chodosh, of the University of Pennsylvania School of Medicine, said "While it is not possible to confirm a causal role for Snail in human breast cancer recurrence until drugs are available to inhibit this pathway, we believe that treatment of patients with pharmacologic agents that block Snail expression or function may be a promising approach to preventing breast cancer relapse."

Of Snail, mice, and women.

Expression of the transcription factors snail, slug, and twist and their clinical significance in human breast cancer.

Posted by Richard at September 20, 2005 10:42 PM

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