Opioid-induced regulation of mu-opioid receptor gene expression in the MCF-7 breast cancer cell line.
The aim of the study was to investigate the presence of opioid receptor types in human breast adenocarcinoma MCF-7 cells and to characterize the changes in MOR expression induced by opioid agonist and antagonist treatment. We have shown that all three types of opioid receptors, but predominantly MOR, are expressed in MCF-7 cells. Selective MOR agonists, morphine, endomorphin-1, and endomorphin-2 downregulated MOR mRNA levels in a concentration- and time-dependent manner, but the effect produced by endomorphins was much stronger. Downregulation was blocked by the opioid antagonist naloxone. Naloxone alone produced a slight increase in MOR gene expression. Immunoblotting with antiserum against MOR-1 confirmed these results at the protein level. The results of our study indicate that, in MCF-7 cells, MOR gene expression is downregulated by opioid agonists and upregulated by opioid antagonists. We propose that the opioid-induced regulation of MOR mRNA expression is mediated by reduced binding of the transcription factors NFkappaB and AP-1 to the promoter region on the MOR gene.
Laboratory of Biomolecular Chemistry, Medical University of Lodz, Mazowiecka 6/8, Lodz, Poland.
Katarzyna
K
Gach
Mariola
M
Piestrzeniewicz
Jakub
J
Fichna
Barbara
B
Stefanska
Janusz
J
Szemraj
Anna
A
Janecka
D000701:Analgesics, Opioid / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009020:Morphine / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014158:Transcription, Genetic
D000701:Analgesics, Opioid; D016328:NF-kappa B; D009292:Narcotic Antagonists; D009842:Oligopeptides; D012333:RNA, Messenger; D017450:Receptors, Opioid, mu; D018808:Transcription Factor AP-1; C105293:endomorphin 1; D009270:Naloxone; C105294:endomorphin 2; D009020:Morphine