Short-chain fatty acids induce acute phosphorylation of the p38 mitogen-activated protein kinase/heat shock protein 27 pathway via GPR43 in the MCF-7 human breast cancer cell line.
The expression of GPR41 and 43, which have recently been identified as G-protein-coupled cell-surface receptors for short-chain fatty acids (SCFAs), was detected in a human breast cancer cell line (MCF-7) by RT-PCR. Acetate, propionate and butyrate induced an increase in intracellular Ca2+ in these cells that was not blocked by treatment with pertussis toxin (PTX). SCFAs significantly reduced forskolin-induced cAMP levels in these cells. The phosphorylation of mitogen-activated protein kinase (MAPK) p38 was selectively increased by SCFAs. The downstream substrate heat shock protein 27 (HSP27) was also phosphorylated by SCFAs at Ser-78 and-82, but not-15. Propionate induced elevations in intracellular Ca2+ and the phosphorylation of p38 were inhibited by the silencing of GPR43 using a specific siRNA. These results suggest that GPR41 and 43 mediate SCFA signaling in mammary epithelial cells and thereby play an important role in their stress management.
Yonezawa
Tomo
T
Department of Animal Physiology, Graduate School of Agricultural Science, Tohoku University, Amamiyamachi, Sendai 981-8555, Japan. yonet@bios.tohoku.ac.jp
Kobayashi
Yosuke
Y
Obara
Yoshiaki
Y
D000085:Acetates / Q000494:pharmacology; D001943:Breast Neoplasms; D002087:Butyrates / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D005232:Fatty Acids, Volatile / Q000494:pharmacology*; D005260:Female; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D037342:Pertussis Toxin / Q000494:pharmacology; D010766:Phosphorylation; D011422:Propionates / Q000494:pharmacology; D020239:Receptor Cross-Talk; D011956:Receptors, Cell Surface / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015290:Second Messenger Systems; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D000085:Acetates; D002087:Butyrates; D002118:Calcium; D005576:Colforsin; D000242:Cyclic AMP; D005232:Fatty Acids, Volatile; D006360:Heat-Shock Proteins; D037342:Pertussis Toxin; D011422:Propionates; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D048051:p38 Mitogen-Activated Protein Kinases; C473103:FFAR2 protein, human; C106262:FFAR3 protein, human