RRC ID 63026
Author Fujii T, Ogasawara M, Kamishikiryo J, Morita T.
Title β-Estradiol Enhanced Secretion of Lipoprotein Lipase from Mouse Mammary Tumor FM3A Cells.
Journal Biol Pharm Bull
Abstract The role of β-estradiol (E2) in lipoprotein metabolism in mammary tumors is unclear, therefore, we investigated the effect of E2 on the secretion of lipoprotein lipase (LPL) from mouse mammary tumor FM3A cells. E2-treated cells increased the secretion of active LPL from FM3A cells in a time- and dose-dependent manner. Activity of mitogen-activated protein kinase (MAPK) was increased in the tumor cells treated with E2, and enhanced secretion of LPL was suppressed by MAPK kinase 1/2 inhibitor, PD98059, extracellular signal-regulated kinase (ERK) 1/2 inhibitor, FR180204, p38 MAPK inhibitor, SB202190, and phosphatidyl inositol 3-kinase (PI3K) inhibitor, LY294002. In addition, the effect of E2 on LPL secretion was markedly suppressed by an inhibitor of mammalian target of rapamycin complex (mTORC) 1 and 2, KU0063794, but were not by a mTORC1 inhibitor, rapamycin. Furthermore, a small interfering RNA (siRNA)-mediated decrease in the expression of rapamycin-insensitive companion of mTOR (Rictor), a pivotal component of mTORC2, suppressed secretion of LPL by E2. These results suggest that the stimulatory secretion of LPL by E2 from the tumor cells is closely associated with an activation of mTORC2 rather than mTORC1 possibly via the MAPK cascade.
Volume 43(9)
Pages 1407-1412
Published 2020-1-1
DOI 10.1248/bpb.b20-00408
PMID 32879215
MeSH Animals Cell Line, Tumor Culture Media / metabolism Estradiol / metabolism* Female Gene Knockdown Techniques Lipid Metabolism / drug effects Lipid Metabolism / physiology Lipoprotein Lipase / metabolism* Lipoproteins / metabolism MAP Kinase Signaling System / drug effects MAP Kinase Signaling System / physiology* Mammary Neoplasms, Animal / pathology* Mechanistic Target of Rapamycin Complex 1 / antagonists & inhibitors Mechanistic Target of Rapamycin Complex 1 / metabolism Mice Mitogen-Activated Protein Kinases / antagonists & inhibitors Mitogen-Activated Protein Kinases / metabolism Morpholines / pharmacology Protein Kinase Inhibitors / pharmacology Pyrimidines / pharmacology Rapamycin-Insensitive Companion of mTOR Protein / antagonists & inhibitors Rapamycin-Insensitive Companion of mTOR Protein / genetics Rapamycin-Insensitive Companion of mTOR Protein / metabolism*
IF 1.863
Human and Animal Cells FM3A(RCB0086)