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γ干扰素对人乳腺癌细胞系增殖、雌二醇受体及雌激素调节蛋白PS2/BCEI的调控作用

Modulation of proliferation, estradiol receptors and estrogen regulated protein PS2/BCEI in human breast cancer cell lines by gamma interferon.

作者信息

Solary E, Prud'homme J F, Gauville C, Magdelenat H, Calvo F

机构信息

Pharmacology Laboratory, Hôpital Saint-Louis, Paris, France.

出版信息

J Biol Regul Homeost Agents. 1991 Jul-Sep;5(3):98-106.

PMID:1763658
Abstract

The effects of recombinant gamma interferon (IFN gamma) on proliferation, estrogen-receptor (ER) content, mRNA level and protein secretion of a breast cancer estrogen-induced protein pS2/BCEI were investigated in two human breast cancer cell lines, ZR75-1 and T47D. Both cell lines have estrogen and progesterone receptors and previously showed HLA class I and class II responses to IFN gamma (Int J Cancer 1990; 45: 1169). An antiproliferative effect of IFN gamma (1000-5000 U/ml) was observed in serum containing medium on ZR75-1 but not on T47D cells. Noninhibitory concentration of IFN gamma (100 U/ml) had sensitising antiproliferative effect with antiestrogens on ZR75-1 cells whereas IFN gamma did not modify the growth inhibition observed in T47D cells with antiestrogens. In serum-free, estradiol-free, phenol-red-free chemically defined medium (Cancer Res 1984; 44: 4553), IFN gamma abolished in ZR75-1 but not in T47D the 30% growth stimulation induced by estradiol. In ZR75-1 cells, IFN gamma induced a transitory 30-50% increase of ER content, as measured by ER-enzymoimmunoassay, at day 2 of culture, and reduced mRNA level and secretion of pS2/BCEI. In T47D cells, a 30-50% decrease of ER content was observed but only when cells were long term cultured (30 weeks) with IFN gamma. In this cell line, no transcription of pS2/BCEI was observed. Antiproliferative action of IFN gamma on ZR75-1 cells is associated with an inhibition of estradiol effects and a reduction of pS2/BCEI mRNA level and protein secretion.

摘要

在两种人乳腺癌细胞系ZR75-1和T47D中,研究了重组γ干扰素(IFNγ)对乳腺癌雌激素诱导蛋白pS2/BCEI的增殖、雌激素受体(ER)含量、mRNA水平及蛋白分泌的影响。这两种细胞系均有雌激素和孕激素受体,且先前已显示对IFNγ有HLA I类和II类反应(《国际癌症杂志》1990年;45: 1169)。在含血清培养基中,观察到IFNγ(1000 - 5000 U/ml)对ZR75-1细胞有抗增殖作用,但对T47D细胞无此作用。IFNγ的非抑制浓度(100 U/ml)与抗雌激素联合对ZR75-1细胞有增敏抗增殖作用,而IFNγ未改变T47D细胞中抗雌激素所观察到的生长抑制作用。在无血清、无雌二醇、无酚红的化学限定培养基中(《癌症研究》1984年;44: 4553),IFNγ消除了ZR75-1细胞中由雌二醇诱导的30%的生长刺激,但对T47D细胞无此作用。在ZR75-1细胞中,通过ER酶免疫测定法检测,IFNγ在培养第2天诱导ER含量短暂增加30 - 50%,并降低pS2/BCEI的mRNA水平及分泌。在T47D细胞中,仅当细胞用IFNγ长期培养(30周)时,观察到ER含量降低30 - 50%。在此细胞系中,未观察到pS2/BCEI的转录。IFNγ对ZR75-1细胞的抗增殖作用与抑制雌二醇作用以及降低pS2/BCEI的mRNA水平和蛋白分泌相关。

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Interferon plus tamoxifen treatment for advanced breast cancer: in vivo biologic effects of two growth modulators.干扰素联合他莫昔芬治疗晚期乳腺癌:两种生长调节剂的体内生物学效应
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