外源性瘦素对裸鼠人乳腺癌移植瘤模型中雌激素受体α和β的调节作用。

Regulation of estrogen receptors alpha and beta in human breast carcinoma by exogenous leptin in nude mouse xenograft model.

机构信息

Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.

出版信息

Chin Med J (Engl). 2010 Feb 5;123(3):337-43.

PMID:20193256

Abstract

BACKGROUND

It is essential to clarify the interactions of hormones during the progression of human breast cancer. This study examined the effects of exogenous human leptin on estrogen receptor (ER) alpha and beta in human breast tumor tissue in a nude mouse xenograft model.

METHODS

We created nude mice xenografts of MCF-7 human breast cancer cells, and randomly divided them into an experimental group and a control group. The mice in experimental group were injected subcutaneously around tumors with human leptin, while the control group were injected with the same dose of normal saline. A real-time RT-PCR assay was developed to quantify the mRNA of ERalpha, beta in the tumor tissues. Western blotting analyses were used to assess the relative quantities of the ERalpha, beta proteins.

RESULTS

Leptin-treated xenografted nude mice were successfully established. The amount of ERalpha mRNA was significantly higher in the leptin group than in the control group (P < 0.01), while the amount of ERbeta mRNA was significantly lower in the leptin group than in the control group (P < 0.01). Western blotting analyses revealed that the ERalpha protein level was significantly higher in the leptin group than in the control group (P < 0.01), while the ERbeta protein level was significantly lower in the leptin group than in the control group (P < 0.01).

CONCLUSIONS

Nude mouse xenograft model can be safely and serviceably treated with human leptin by subcutaneous injections around tumor. ERalpha, beta were both targets of leptin in breast cancer. Leptin can up-regulate the expression of ERalpha and down-regulate the expression of the ERbeta in human breast tumor.

摘要

背景

阐明激素在人类乳腺癌进展过程中的相互作用至关重要。本研究在裸鼠异种移植模型中检测了外源性人瘦素对人乳腺癌组织中雌激素受体（ER）α和β的影响。

方法

我们创建了 MCF-7 人乳腺癌细胞的裸鼠异种移植，并将其随机分为实验组和对照组。实验组小鼠在肿瘤周围皮下注射人瘦素，对照组小鼠注射相同剂量的生理盐水。采用实时 RT-PCR 法检测肿瘤组织中 ERα、β的 mRNA 表达量，采用 Western blot 分析评估 ERα、β蛋白的相对含量。

结果

成功建立了瘦素处理的异种移植裸鼠模型。与对照组相比，瘦素组的 ERα mRNA 量显著升高（P < 0.01），而 ERβ mRNA 量显著降低（P < 0.01）。Western blot 分析显示，瘦素组的 ERα 蛋白水平显著高于对照组（P < 0.01），而 ERβ 蛋白水平显著低于对照组（P < 0.01）。