Potent stimulatory effect of interleukin-1 alpha on apolipoprotein D and gross cystic disease fluid protein-15 expression in human breast-cancer cells.
To better understand the multiple hormonal control of the expression of apolipoprotein D (apo-D) and gross cystic disease fluid protein-15 (GCDFP-15, also designated prolactin-inducible protein), which are 2 major proteins found in benign breast-disease fluid, we investigated their regulation by interleukin-1 alpha (IL-1 alpha) in the presence or absence of steroid hormones in ZR-75-1 human breast cancer cells. Exposure of these cells to IL-1 alpha decreased basal cell proliferation by half and markedly reduced the mitogenic action of 17 beta-estradiol (E2), the half-maximal inhibitory effect being exerted at 1.5 pM. In parallel, IL-1 alpha stimulated apo-D and GCDFP-15 secretion with a similar potency. The antiproliferative effect of IL-1 alpha was additive to the inhibition of cell proliferation caused by dihydrotestosterone (DHT) or the glucocorticoid dexamethasone (DEX). In parallel, IL-1 alpha-induced stimulation of apo-D and GCDFP-15 secretion was additive to that exerted by DHT or DEX. The sensitivity of the apo-D and GCDFP-15 responses to the stimulatory action of DHT or DEX was not changed by the presence of IL-1 alpha. IL-1 alpha also increased apo-D and GCDFP-15 mRNA levels. The present findings demonstrate the potent stimulatory effect of IL-1 alpha on basal as well as androgen- and glucocorticoid-induced apo-D and GCDFP-15 expression. The present data strongly suggest that IL-1 alpha and steroids may modulate the secretion of these 2 proteins through different transduction pathways.
Blais
Y
Y
Medical Research Council Group in Molecular Endocrinology, CHUL Research Center, Québec, Canada.
Sugimoto
K
K
Carriere
M C
MC
Haagensen
D E
DE
Labrie
F
F
Simard
J
J
D001053:Apolipoproteins / Q000096:biosynthesis* / Q000235:genetics; D053399:Apolipoproteins D; D001483:Base Sequence; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D002455:Cell Division; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology; D005938:Glucocorticoids / Q000494:pharmacology; D006023:Glycoproteins; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D026901:Membrane Transport Proteins; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D014407:Tumor Cells, Cultured
C024328:APOD protein, human; D001053:Apolipoproteins; D053399:Apolipoproteins D; D002352:Carrier Proteins; D005938:Glucocorticoids; D006023:Glycoproteins; D007375:Interleukin-1; D026901:Membrane Transport Proteins; D009363:Neoplasm Proteins; D015345:Oligonucleotide Probes; C488892:PIP protein, human; D012333:RNA, Messenger