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Overexpressed protein converts noninvasive breast cancer into invasive disease
Date:9/8/2009

e broader implications relating to the mechanism of invasion and metastasis in other types of cancer," Yu said.

Unzipping cancer cells

The team set out to address a longstanding puzzle, Yu said. ErbB2, an oncoprotein that promotes metastasis, is overexpressed in 50 to 60 percent of the noninvasive breast cancer known as ductal carcinoma in situ (DCIS). However, that same protein is overexpressed in only about 25 percent of invasive breast cancers, which seemed counterintuitive.

In a series of lab experiments, Yu and colleagues showed that overexpression of ErbB2 accompanied by overexpression of 14-3-3ζ can change DCIS into invasive breast cancer. This only occurs in about half of ErbB2-overexpressing DCIS, the team found, explaining the numerical puzzle.

Overexpression of ErbB2 converts normal breast duct cells into abnormal cells that reproduce quickly, are capable of moving, and resist programmed cell death that usually kills aberrant cells. What prevents these DCIS cells from becoming invasive, Yu said, is that they are locked together in zipper-like fashion by the cell surface protein E-cadherin, a trait known as cell-cell adhesion.

"Overexpression of 14-3-3ζ is the catalyst for a molecular pathway that strips E-cadherin from the cells, setting the cells loose from each other," Yu said. These cells also change in appearance from blunt normal breast duct cells to a narrow spindle shape characteristic of a mesenchymal-like cell.

Double overexpression reduces survival time

Epithelial cells line an organ or its cavities and are generally immobile. Mesenchymal cells are mobile and can differentiate into many different cell types, for example, to repair injury. Epithelial-mesenchymal transition is known to repress E-cadherin, decrease cell-cell adhesion and increase a cell's capacity to move. An estimated 80 percent of all solid tumors are carcinomas, cancers of the epithelial tissue.


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Contact: Scott Merville
smerville@mdanderson.org
713-792-0661
University of Texas M. D. Anderson Cancer Center
Source:Eurekalert

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