Gene Identified That Regulates Breast Cancer Metastasis

A key gene involved in the spread of breast cancer throughout the body has been identified. Previously, the function of that gene was unknown.

Expression of the gene, KLF17, together with another gene (Id1) known to regulate breast cancer metastasis, accurately predicted whether the disease would spread to the lymph nodes.

In a study, which appears in the October 2009 on-line issue of Nature Cell Biology, Qihong Huang, M.D., Ph.D., assistant professor at the Wistar Institute (Philadelphia, PA, USA), and colleagues introduced a genetic screen targeting 40,000 mouse genes into mammary tumor cells that do not usually spread, and then transplanted those cells to the mammary fat pads in mice where they would be expected to remain. Through RNA interference (RNAi) technology, they then reduced the expression of a metastasis-suppressor gene in five mice, one of which developed lung metastases in seven weeks. RNA retrieved from the metastasized cells corresponded to KLF17.

To determine whether KLF17 played a similar role in human breast-cancer metastasis, the scientists knocked down KLF17 expression in a tagged human-breast-cancer cell line and then transplanted these cells--along with a control group still expressing KLF17--into mammary fat pads of mice. Within eight to 10 weeks, lung metastases developed in the KLF17-deficient cells, whereas the control cell set did not metastasize, demonstrating that knockdown of KLF17 expression also promotes the spread of human breast-cancer cells.

In collaboration with Professor Louise C. Showe, Ph.D. at the Wistar Institute, the scientists found that the gene Id1 was upregulated in KLF17 knockdown cells and down-regulated in KLF17 overexpressing cells. Recent findings suggest that Id1 is deregulated in various types of cancers and is important in the development of embryonic stem cell-like phenotypes in cancer cells.

Further characterization of KLF17 is an ongoing subject of study for Wistar investigators. "We are continuing to examine ways to activate KLF17 and the methods by which that process slows or prevents cancer metastasis,” Prof. Huang said.

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