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Cells lining milk ducts hold key to spread of common form of breast cancer
Date:5/5/2008

ak and her colleagues focused on myoepithelial cells, which form part of the lining of the milk ducts and are involved in breast development, as well as impeding the growth and invasiveness of some cancer cells. To study what role, if any, these cells play in DCIS, the researchers worked with a specially engineered line of cells known as MCFDCIS.

When injected in laboratory animals, the MCFDCIS cells formed DCIS-like tissue that developed into invasive tumors, providing a good model of what happens in human disease. When researchers injected both MCFDCIS and myoepithelial cells into the mice, DCIS tumors arose, but they were confined to the ducts. When they injected MCFDCIS cells and fibroblasts -- cells found in milk ducts and other connective tissue -- the resulting DCIS tumors broke into the walls of the ducts.

"These findings made it clear that fibroblasts promote tumor growth and invasion, and normal myoepithelial cells suppress it," Polyak remarks. But when certain genes in the myoepithelial layer become under- or overactive, the layer breaks down and disappears, enabling tumor cells to escape.

To identify which genes are affected and what causes their activity level to change, Polyaks team surveyed the activity of thousands of genes in myoepithelial and DCIS cells using advanced SAGE (Serial analysis of gene expression) technology. When DCIS tumors trespass into the lining of the ducts, the activity level of several myoepthelial cell genes is abnormal -- specifically the TGF Beta, Hedgehog, and p63 genes as well as genes that help myoepithelial cells stick to "basement" cells on the ducts outer layer. The effect is a cacaphony of erratic signals and haywire activity that prevents myoepithelial cells from fully maturing and forming an effective barrier to DCIS.

"We found a constant, complex interplay of signals among these genes, both within myoepithelial cells themselves, and between myoepithelial cells and their neighbors
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Contact: Robbin Ray
robbin_ray@dfci.harvard.edu
617-632-4090
Dana-Farber Cancer Institute
Source:Eurekalert

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