- Tomoyasu Fujii (Department of Biochemistry, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University / firstname.lastname@example.org)
Department of Biochemistry, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University
Progesterone (P4) is a corpus luteum hormone associated with the development of the mammary gland and uterus. The actions of P4 on lipid metabolism in breast cancer are unclear. In this study, we investigated medroxyprogesterone acetate (MPA) on the secretion of lipoprotein lipase (LPL) from mouse mammary tumor FM3A cells. The tumor cells were incubated with MPA and other agents. The treated cells were used in the mitogen-activated protein kinase (MAPK) and LPL activity assay. The supernatant was used in the LPL activity assay and western blotting. The increased secretion of LPL in the tumor cells treated with MPA was observed. The MPA-stimulated secretion of LPL was suppressed by a protein kinase A (PKA) inhibitor. The activity of MAPK increased in the tumor cells treated with MPA, and various MAPK inhibitors suppressed the stimulatory secretion of LPL. The effect of MPA on LPL secretion was markedly suppressed by an inhibitor of the mechanistic target of rapamycin complex (mTORC) 1 and 2, KU0063794, but not the mTORC1 inhibitor, rapamycin. Furthermore, a small interfering RNA-mediated decrease in Rictor's expression, a pivotal component of mTORC2, suppressed the stimulatory secretion of LPL. These results suggest that the stimulatory secretion of LPL in the tumor cells treated with MPA is closely associated with activation of mTORC2, possibly via the MAPK signaling associated with PKA activation.