The scientists then used genetic methods to test the breast cancer cells in a mouse model that the scientists genetically altered to increase or over-express levels of DLC1. These mice developed tumors, and when they examined the cells that over-express DLC1, they also discovered that the cells could move faster than normal cells, they reproduced faster, and could grow without normal cell contacts ??“ what is called anchorage independence.

???Taken together, these studies show cells that over-express DLC1 have enhanced cell survival and blockage of death signals, all of the characteristics required for successful tumor formation,??? says Kumar.

But when the research team engineered a form of the DLC1 protein missing the crucial modification site, the protein could no longer block cell death signals and could no longer form tumors.

Kumar says that since DLC1 is a small protein and the research team has identified exactly how it becomes modified by Pak1, it may be possible in the future to block its activity through the use of drugs designed to inhibit its activity. Such inhibitors might restore the cell??™s normal recognition of cell death signals, Kumar says.

However, he adds that more work needs to be done to understand how over-expression of DLC1 contributes to the development of breast cancer.

M. D. Anderson scientists Ratna Vadlamudi, Ph.D., Rozita Bagheri-Yarmand, Ph.D., Zhibo Yang, Ph.D., Seetharaman Balasenthil, Ph.D., Diep Nguyen, Aysegul Sahin, M.D., and Petra den Hollander, contributed to the study. The research was supported by NIH grants.

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