ESTRADIOL DOWN-REGULATES THE MANNOSE-6-PHOSPHATE INSULIN-LIKE GROWTH FACTOR-II RECEPTOR GENE AND INDUCES CATHEPSIN-D IN BREAST-CANCER CELLS - A RECEPTOR SATURATION MECHANISM TO INCREASE THE SECRETION OF LYSOSOMAL PROENZYMES
ESTRADIOL DOWN-REGULATES THE MANNOSE-6-PHOSPHATE INSULIN-LIKE GROWTH FACTOR-II RECEPTOR GENE AND INDUCES CATHEPSIN-D IN BREAST-CANCER CELLS - A RECEPTOR SATURATION MECHANISM TO INCREASE THE SECRETION OF LYSOSOMAL PROENZYMES
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DOI：
10.1210/mend-5-6-815
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发表时间：
1991-06-01
影响因子：
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通讯作者：
ROCHEFORT, H
中科院分区：
文献类型：
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作者：
MATHIEU, M;VIGNON, F;ROCHEFORT, H
我们研究了雌二醇对不同乳腺癌细胞系中甘露糖-6-磷酸（Man-6-P）/胰岛素样生长因子-II（IGF-II）受体浓度的调节。以H5.1 cDNA为探针，采用北方印迹法检测mRNA水平。蛋白质水平通过蛋白质配体印迹、通过与总膜制备物上的[I-125]组织蛋白酶原-D的结合饱和度以及通过S-35标记的蛋白质的免疫沉淀来测定。在三种雌激素受体阳性细胞系（MCF 7，T47 D和ZR 75 -1）中，雌二醇特异性降低Man-6-P/IGF-II受体蛋白和mRNA的稳态水平。此外，在不同的细胞系和原代培养的正常乳腺细胞中，前组织蛋白酶D的分泌与Man-6-P/IGF-II受体的蛋白和mRNA水平呈负相关。我们得出结论，雌二醇下调乳腺癌细胞中的Man-6-P/IGF-II受体。由于它的两个配体，血管紧张素原-D和IGF-II，是由雌激素诱导的，我们建议，在雌激素治疗后的Man-6-P/IGF-II受体变得饱和。这个模型可能解释了先前描述的雌激素诱导的分泌的前组织蛋白酶D和其他溶酶体酶原路由相同的运输系统。
We have studied the regulation by estradiol of the mannose-6-phosphate (Man-6-P)/insulin-like growth factor-II (IGF-II) receptor concentration in different breast cancer cell lines. The mRNA level was assayed by Northern blot using the H5.1 cDNA probe. The protein level was assayed by Western ligand blot, by binding saturation with [I-125]procathepsin-D on total membrane preparations, and by immunoprecipitation of S-35-labeled proteins. In three estrogen receptor-positive cell lines (MCF7, T47D, and ZR75-1), estradiol specifically decreased the steady state level of the Man-6-P/IGF-II receptor protein and mRNA. Moreover, in different cell lines and in primary culture of normal mammary cells, the secretion of procathepsin-D was inversely correlated with the level of Man-6-P/IGF-II receptor protein and mRNA.We conclude that estradiol down-regulates the Man-6-P/IGF-II receptor in breast cancer cells. Since two of its ligands, procathepsin-D and IGF-II, are induced by estrogen, we propose that the Man-6-P/IGF-II receptor becomes saturated after estrogen treatment. This model might explain the previously described estrogen-induced secretion of procathepsin-D and other lysosomal proenzymes routed by the same transport system.