Researchers Locate Breast Cancer Gene

      ANN ARBOR, Mich. -- In the midst of Breast Cancer Awareness Month, a recently published study in the journal Cancer Research sheds some light on the genetics of inflammatory breast cancer.

      IBC, regarded as the most deadly form of locally advanced breast cancer, accounts for 6 percent of all breast cancer diagnoses in the U.S. each year.

      IBC spreads so quickly it often reaches lymph nodes or other parts of the body by the time it''s diagnosed, leaving only 45 percent of women with the disease alive and disease free after five years.

      Researchers at the University of Michigan have discovered the gene responsible for IBC, which helps to explain the disease and may aid in its treatment.

      "It''s really encouraging," said Kenneth van Golen, co-author and research investigator in the department of internal medicine. "Clinically this disease has been in literature for 120 years, but up until 1999, nobody knew anything about the genetics of it."

      Author and University of Michigan internal medicine associate Prof. Sofia Merajver said the team discovered that the gene, RhoC GTPase, was particularly active in a sample of breast cancer.

      "By taking the gene and manipulating it, there is proof of principle that this gene is actually causing the tumor," she said.

      RhoC genes are present in all cells and are necessary for cell life, but can cause cancer when the production is overactive. In normal gene expression, it helps to arrange the cytoskeleton of the cell and allow for the cell to move and change shape.

      "When (RhoC genes are) overly active it makes the cell very invasive with high mobility and it doesn''t seem to respect the environment," Merajver said.

      The high mobility allows the cancer to move throughout the body very quickly and spread to lymph nodes, blood and anywhere else in the body.

      "Patients have tumor cells that are literally crawling through the body," van Golen said.

      The researchers inserted the RhoC gene into normal breast cells and compared the results with cells from an IBC tumor tissue sample.

      "We identified genes that were important in inflammatory breast cancer," van Golen said. "We''ve taken one of the genes and put it into a normal breast cell and we''ve basically re-made the cancer phenotype. We''ve made the normal cell look like cancer."

      The tests were performed in test tubes and then in laboratory mice. About 25 percent of the mice that were given the RhoC cells formed tumors while none of the mice that received normal breast cells had tumors.

      "We found that the cancer we created in test tubes caused cancer in the animals." Merajver said. "Sometimes you can cause things in the laboratory that aren''t realistic in animals."

      But the scientists believe that there are other key genetic factors involved in forming the tumors. In a previous study the team found that the under expression of a tumor suppressor gene called LIBC (Lost in Inflammatory Breast Cancer), may also be a cause. The team will continue the research to find a molecule either upstream or downstream from the RhoC gene, or even the gene itself that will deactivate the gene.

      While there are no treatments based on the discovery of the gene available clinically, they are being developed in the laboratory.

      "We want to get more specific function and eventually cure breast cancer," said health science research associate Zhi-Fen Wu. "We got lots of good data. This paper is just a beginning."

      The study was published in the Oct. 15 issue of the journal.