Interleukin-4 and interleukin-13 inhibit estrogen-induced breast cancer cell proliferation and stimulate GCDFP-15 expression in human breast cancer cells
Interleukin-4 and interleukin-13 inhibit estrogen-induced breast cancer cell proliferation and stimulate GCDFP-15 expression in human breast cancer cells
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DOI：
10.1016/0303-7207(96)03843-9
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发表时间：
1996-07-23
影响因子：
4.1
通讯作者：
Simard, J
中科院分区：
文献类型：
--
作者：
Blais, Y;Gingras, S;Simard, J
人乳腺癌中经常有炎性细胞浸润，炎性细胞分泌多种细胞因子，这些细胞因子可调节免疫细胞和肿瘤细胞的活性。本研究旨在检测白细胞介素-4（IL-4）和白细胞介素-13（IL-13）在人乳腺癌细胞中的潜在作用。ZR-75-1乳腺癌细胞暴露于IL-4或IL-13 10天，17 β-雌二醇的促有丝分裂作用的幅度分别降低了75%和55%，而这些细胞因子未能改变基底细胞增殖。这些细胞因子在T-47 D细胞中也发挥类似的作用。暴露于IL-4或IL-13显著增加ZR-75-1和T-47 D细胞中的总囊性病液蛋白-15（GCDFP-15）释放。IL-4和IL-13对GCDFP-15分泌的半最大刺激作用在孵育10天的T-47 D细胞中分别以16 +/- 3 pM和91 +/- 8 pM的值发挥。IL-13的效果是不加性的IL-4引起的，而刺激GCDFP-15释放这些白细胞介素是加性的雄激素双氢睾酮和合成的糖皮质激素地塞米松的最大有效浓度所施加的。此外，ZR-75-1细胞暴露于IL-4和IL-13分别使GCDFP-15 mRNA水平增加5.5倍和6.0倍。目前的结果表明，IL-4和IL-13可以减少雌激素诱导的乳腺癌细胞增殖，并诱导乳腺癌标志物的表达，从而强烈表明，乳腺癌细胞是IL-4和IL-13作用的目标。
Human breast carcinomas are frequently infiltrated by inflammatory cells secreting several cytokines which may regulate the activity of both immune cells and neoplastic cells. The present study was designed to examine the potential action of interleukin-4 (IL-4) and interleukin-13 (IL-13) in human breast cancer cells. Exposure of ZR-75-1 breast cancer cells to IL-4 or IL-13 for 10 days decreased the amplitude of the mitogenic action of 17 beta-estradiol by 75% and 55%, respectively, while these cytokines failed to change basal cell proliferation. These cytokines also exerted a similar action in T-47D cells. Exposure to IL-4 or IL-13 markedly increased gross cystic disease fluid protein-15 (GCDFP-15) release in both ZR-75-1 and T-47D cells. The half-maximal stimulatory effects of IL-4 and IL-13 on GCDFP-15 secretion were exerted at respective values of 16 +/- 3 pM and 91 +/- 8 pM in T-47D cells incubated for a period of 10 days. The effect of IL-13 was not additive to that elicited by IL-4, whereas the stimulation of GCDFP-15 release by these interleukins were additive to that exerted by maximally effective concentrations of the androgen dihydrotestosterone and the synthetic glucocorticoid dexamethasone. Furthermore, exposure of ZR-75-1 cells to IL-4 and IL-13 increased GCDFP-15 mRNA levels by 5.5- and 6.0-fold, respectively. The present results demonstrate that IL-4 and IL-13 may decrease estrogen-induced breast cancer cell proliferation and induce the expression of a breast cancer marker, thus strongly suggesting that breast cancer cells are targets of both IL-4 and IL-13 action.