Protein Kinase D1 regulates MMP expression and inhibits breast cancer cell invasion

Breast Cancer Research 2009, 11:R13doi:10.1186/bcr2232

Tim Eiseler , Heike Doeppler , Irene K Yan , Steve Goodison and Peter Storz

We found that the serine/threonine kinase Protein Kinase D1(PKD1) is highly expressed in ductal epithelial cells of normal human breast tissue, but is reduced in its expression in >95% of all analyzed samples of human invasive breast tumors. Additionally, PKD1 is not expressed in highly invasive breast cancer cell lines, whereas non- or very low-invasive breast cancer cell lines express PKD1. Our results further implicate that in MDA-MB-231 cells PKD1 expression is blocked by epigenetic silencing via DNA methylation. The re-expression of constitutively-active PKD1 in MDA-MB-231 cells drastically reduced their ability to invade in 2D and 3D cell culture. Moreover, MCF-7 cells acquired the ability to invade in 2D and 3D cell culture when PKD1 expression was knocked-down by shRNA. PKD1 also regulated the expression of breast cancer cell matrix-metalloproteinases MMP-2, MMP-7, MMP-9, MMP-10, MMP-11, MMP-13, MMP-14 and MMP-15, providing a potential mechanism for PKD1 mediation of the invasive phenotype.