DOK1/PPARgamma pathway mediates anti-tumor ability of all-trans retinoic acid in breast cancer MCF-7 cells.

Previous studies have showed the anticancer effect of the all-trans retinoic acid (ATRA) in many tumors including breast cancer; however, the underlying molecular mechanism is still poorly understood. This study experimentally revealed that ATRA treatment inhibited MCF-7 cell proliferation and promoted its apoptosis, along with an enhanced expression of docking protein 1 (DOK1). ATRA's effects on cell proliferation and apoptosis were prevented by DOK1 knockdown. In addition, the genetic silence of DOK1 can inhibit PPARγ expression and its activity. Moreover, inactivation of PPARγ by its specific inhibitor GW9662 reversed the impacts of ATRA on cell proliferation and apoptosis. Taken together, these results indicate that ATRA-enhanced expression of DOK1 activates PPARγ leading to inhibition of cell proliferation and enhancement of cell apoptosis in MCF-7 cell.