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P21-Activated kinase 1 coordinates aberrant cell survival and pericellular proteolysis in a three-dimensional culture model for premalignant progression of human breast cancer.


ABSTRACT: Overexpression of p21-activated kinase 1 (PAK1) occurs during the progression of human breast cancer. We have investigated the role of PAK1 in the premalignant progression of the MCF10 series of human breast epithelial cell lines. Levels of PAK1 expression and activation increased with premalignant progression, and expression of dominant-negative (DN) PAK1 reduced both cell proliferation and migration/invasion. In three-dimensional (3D) overlay cultures in reconstituted basement membrane, the MCF10 series produced an in vitro model for premalignant progression. MCF10AneoT cells formed a hyperplastic morphology in which some spheroids developed abnormal lumens. The MCF10.AT1 line exhibited an atypical hyperplastic morphology of abnormal spheroid clusters that did not form lumens. The MCF10.

SUBMITTER: Li Q 

PROVIDER: S-EPMC2288538 | biostudies-literature | 2008 Apr

REPOSITORIES: biostudies-literature