How the Study Was Conducted: The research team reduced the expression of the SLUG gene in human-derived breast cells and then used cell-sorting techniques to separate the cells into groups of luminal, basal, and stem cells. Next, they used mathematical modeling to measure the rate and frequency that each of the three cell types changed into another cell type. By comparing the rates between control cells and cells in which SLUG was reduced, the team was able to determine the role of SLUG in luminal-, basal-, and stem-cell transitions.
To test the result of their mathematical model, the research team examined and compared breast-tissue samples from mice in two groups: a control group with normal SLUG and an experimental group that did not express SLUG. Mammary glands from the experimental and control groups were analyzed for changes in structure, the amount and distribution of luminal and basal cells in the gland, and whether these cells had stem-cell activity.
Results: The SLUG-deficient mice exhibited defects in breast-cell differentiation. The mammary glands of these mice had too many luminal cells and defective basal cells that had luminal-cell characteristics. The control group of normal mice had a normal ratio of luminal to basal cells.
The SLUG-deficient mice showed defects in stem-cell function: Specifically, tumor formation and tissue regeneration was inhibited, an indication of defective stem cells, suggesting that SLUG was necessary to maintain normal luminal and basal cells within the mammary gland.
Additionally, SLUG-deficient cells when transplanted could not regenerate the mammary gland of the mouse, suggesting that SLUG is necessary for mammary stem-cell function. Tumor formation was also inhibited in SLUG-deficient mice
|Contact: Siobhan Gallagher|
Tufts University, Health Sciences Campus