Interleukin-6 inhibits the potent stimulatory action of androgens, glucocorticoids and interleukin-1 alpha on apolipoprotein D and GCDFP-15 expression in human breast cancer cells.
Our study was designed to investigate the potential interaction between steroid hormones and interleukin-6 (IL-6) in the regulation of apolipoprotein D (apo-D) and gross cystic disease fluid protein 15 (GCDFP-15) expression in ZR-75-1 human breast cancer cells. We first observed that exposure to IL-6 for 6-14 days decreased basal apo-D and GCDFP-15 secretion by 50% and 23%, respectively. In the same experiment, such treatment with IL-6 decreased cell proliferation by approximately 40% after 6 and 14 days of incubation. Exposure to IL-6 markedly decreased dihydrotestosterone (DHT)-induced apo-D and GCDFP-15 release, with a half-maximal effect measured at 13 U/ml. A similar inhibitory action of IL-6 was observed on the glucocorticoid dexamethasone (DEX)-induced apo-D and GC-DFP-15 secretion. The sensitivity of the apo-D and GCDFP-15 response to the stimulatory action of DHT or DEX was, however, not changed by concomitant exposure to IL-6. The inhibitory effect of IL-6 on the secretion of these two biochemical markers was additive to that of 17 beta-estradiol. In addition, IL-6 blocked the stimulatory effect of interleukin-1 alpha (IL-1 alpha) on apo-D and GCDFP-15 secretion. Our results show that IL-6 is a potent inhibitory of basal as well as androgen-, glucocorticoid- and IL-1 alpha-induced apo-D and GCDFP-15 secretion in ZR-75-1 human breast cancer cells, while cell proliferation is inhibited by this cytokine.
Blais
Y
Y
Medical Research Council Group in Molecular Endocrinology, CHUL Research Center, Québec, Canada.
Sugimoto
K
K
Carrière
M C
MC
Haagensen
D E
DE
Labrie
F
F
Simard
J
J
D000728:Androgens / Q000502:physiology; D001053:Apolipoproteins / Q000096:biosynthesis* / Q000378:metabolism; D053399:Apolipoproteins D; D001943:Breast Neoplasms / Q000378:metabolism*; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D003907:Dexamethasone / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D013196:Dihydrotestosterone / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004347:Drug Interactions; D004958:Estradiol / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D005938:Glucocorticoids / Q000502:physiology; D006023:Glycoproteins; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors*; D015850:Interleukin-6 / Q000494:pharmacology*; D007700:Kinetics; D026901:Membrane Transport Proteins; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000378:metabolism; D013268:Stimulation, Chemical; D014407:Tumor Cells, Cultured / Q000187:drug effects
C024328:APOD protein, human; D000728:Androgens; D001053:Apolipoproteins; D053399:Apolipoproteins D; D002352:Carrier Proteins; D004965:Estrogen Antagonists; D005938:Glucocorticoids; D006023:Glycoproteins; D007375:Interleukin-1; D015850:Interleukin-6; D026901:Membrane Transport Proteins; D009363:Neoplasm Proteins; C488892:PIP protein, human; D013196:Dihydrotestosterone; D004958:Estradiol; D003907:Dexamethasone