Potent stimulatory effect of interleukin‐1α on apolipoprotein D and gross cystic disease fluid protein‐15 expression in human breast‐cancer cells

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Abstract
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 breastdisease fluid, we investigated their regulation by interleukin‐Iα (IL‐Iα) in the presence or absence of steroid hormones in ZR‐75‐I human breast cancer cells. Exposure of these cells to IL‐Iα decreased basal cell proliferation by half and markedly reduced the mitogenic action of 17β‐estradiol (E2), the halfmaximal inhibitory effect being exerted at 1.5 pM. In parallel, IL‐Iα stimulated apo‐D and GCDFP‐15 secretion with a similar potency. The antiproliferative effect of IL‐Iα was additive to the inhibition of cell proliferation caused by dihydrotestosterone (DHT) or the glucocorticoid dexamethasone (DEX). In parallel, IL‐Iα‐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‐Iα. IL‐Iα also increased apo‐D and GCDFP‐15 mRNA levels. The present findings demonstrate the potent stimulatory effect of IL‐Iα on basal as well as androgen‐ and glucocorticoid‐induced apo‐D and GCDFP‐15 expression. The present data strongly suggest that IL‐Iα and steroids may modulate the secretion of these 2 proteins through different transduction pathways.

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