Regulation of gene expression in MDAMB231 breast cancer cells by Parvin-beta in 2D vs 3D culture conditions

Parvin-beta is a focal adhesion protein downregulated in human breast cancer cells. Loss of Parvin-beta contributes to increased integrin-linked kinase activity, cell-matrix adhesion, and invasion through the extracellular matrix in vitro. The effect of ectopic Parvin-beta expression on the transcriptional profile of MDA-MB-231 breast cancer cells, which normally do not express Parvin-beta was evaluated. Particular emphasis was placed upon propagating MDA-MB-231 breast cancer cells in three-dimensional culture matrices. Gene expression profiles of vector control and Parvin-beta transfected MDA-MB-231 cells cultured on (A) monomeric type I collagen coated plastic, (B) embedded in a type I collagen gel, and (C) embedded in basement membrane (growth factor reduced Matrigel), were compared. Interestingly, Parvin-beta re-expression in MDA-MB-231 cells increased the mRNA expression, serine 82 phosphorylation (mediated by CDK9), and activity of the nuclear hormone receptor, peroxisome proliferator-activated receptor gamma (PPARgamma) and a concomitant increase in lipogenic gene expression as a downstream effector of PPARgamma. Importantly, Parvin-beta suppressed breast cancer growth in vivo with associated decreased proliferation. These data suggest that Parvin-beta might influence breast cancer progression..

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Johnstone CN, Mongroo PS, Rich AS, Schupp M, Bowser MJ, Delemos AS, Tobias JW, Liu Y, Hannigan GE, Rustgi AK