The Pak4 protein kinase is required for oncogenic transformation of MDA-MB-231 breast cancer cells.

The Pak4 protein kinase, normally expressed at low level in the mammary gland, is commonly overexpressed in breast cancer. Overexpression of Pak4 transforms mouse mammary epithelial cells in vitro and renders these cells tumorigenic in athymic mice in vivo. Here we show that Pak4 is also required for oncogenic transformation of the human breast cancer cell line MDA-MB-231. These high Pak4-expressing human breast cancer cells form highly disorganized three-dimensional (3D) structures in vitro and readily give rise to orthotopic xenograft tumors in nude mice. We have found that when Pak4 levels are reduced, MDA-MB-231 cells exhibit decreased proliferation and migration in vitro, as well as gross restoration of normal 3D mammary acinar organization, the latter in association with a strong induction of apoptosis. Similarly, Pak4 knockdown suppresses MDA-MB-231 breast xenograft tumor formation in nude mice in vivo. These results indicate that Pak4 has a key role in the oncogenic transformation of breast cells.