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人乳腺癌细胞MCF-7中I型生长因子受体的mRNA表达:雌二醇和他莫昔芬的调控作用

mRNA expression of the type I growth factor receptors in the human breast cancer cells MCF-7: regulation by estradiol and tamoxifen.

作者信息

Revillion Françoise, Pawlowski Valérie, Lhotellier Valérie, Louchez Marie-Michèle, Peyrat Jean-Philippe

机构信息

Laboratoire d'Oncologie Moléculaire Humaine, Centre Oscar Lambret, 3 rue Frédéric Combemale, BP 309, 59020 Lille, France.

出版信息

Anticancer Res. 2003 Mar-Apr;23(2B):1455-60.

PMID:12820409
Abstract

BACKGROUND

We recently confirmed, in a series of 365 human breast cancers, that EGFR and c-erbB-2 were associated with estradiol receptors (ER) and/or progesterone receptors (PgR)-negative tumors. Conversely, we demonstrated that c-erbB-3 and c-erbB-4 were positively related to ER and PgR. In the present paper, we simultaneously quantified, for the first time, the mRNA expression of these four receptors in response to estradiol and 4-hydroxy-tamoxifen in the prototypical ER-positive human breast cancer cell line MCF-7.

MATERIALS AND METHODS

The mRNA expression of the type I growth factor receptors was quantified with a one-step real-time RT-PCR assay.

RESULTS

Estradiol down-regulates the mRNA expression of the four receptors. The EGFR decrease is maximal (30% under the control) for 10(-11) M estradiol. For the three other receptors, the decrease (50% under the control) in mRNA expression is maximal with 10(-9) M. These effects are completely abolished by 4-OH tamoxifen at 10(-6) M.

CONCLUSION

In MCF-7 cells, we demonstrate that c-erbB-4 is down-regulated by estradiol and up-regulated by 4-OH tamoxifen, and confirm that the three other receptors followed the same pattern of expression.

摘要

背景

我们最近在365例人类乳腺癌中证实,表皮生长因子受体(EGFR)和c-erbB-2与雌激素受体(ER)和/或孕激素受体(PgR)阴性肿瘤相关。相反,我们证明c-erbB-3和c-erbB-4与ER和PgR呈正相关。在本文中,我们首次同时定量了在典型的ER阳性人乳腺癌细胞系MCF-7中,这四种受体对雌二醇和4-羟基他莫昔芬的mRNA表达。

材料与方法

采用一步实时逆转录聚合酶链反应(RT-PCR)法对I型生长因子受体的mRNA表达进行定量。

结果

雌二醇下调这四种受体的mRNA表达。对于10^(-11) M的雌二醇,EGFR的降低幅度最大(比对照低30%)。对于其他三种受体,mRNA表达的降低(比对照低50%)在10^(-9) M时最大。这些作用在10^(-6) M的4-羟基他莫昔芬作用下完全被消除。

结论

在MCF-7细胞中,我们证明c-erbB-4被雌二醇下调,被4-羟基他莫昔芬上调,并证实其他三种受体也遵循相同的表达模式。

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