Modulation of EGFR and neu expression by n-6 and n-9 high-fat diets in experimental mammary adenocarcinomas.

Modulation of EGFR and neu expression by n-6 and n-9 high-fat diets in experimental mammary adenocarcinomas.
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n-6 和 n-9 高脂肪饮食对实验性乳腺癌中 EGFR 和 neu 表达的调节。

DOI:
10.3892/or.10.5.1417
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发表时间:
2003
期刊:
影响因子:
4.2
通讯作者:
E. Escrich
E. Escrich
中科院分区:
医学3区
文献类型:
--
作者:
R. Moral;M. Solanas;Gemma García;R. Colomer;E. Escrich

文献摘要

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在这项研究中,我们研究了膳食单不饱和脂质和多不饱和脂质对 7,12-二甲基苯并(α)蒽 (DMBA) 诱导的乳腺肿瘤发生的影响,以及作为这种影响机制的 c-erbB1/EGFR 和 c-erbB2/neu 表达的调节。两组 Sprague-Dawley 大鼠均接受单剂量 DMBA。按照起始促进实验设计,系列 1 的动物被喂食半合成低脂或高脂玉米油饮食。系列2的大鼠在乳腺癌的促进阶段被喂食低脂或不同的高脂饮食(富含玉米油或富含橄榄油)。高玉米油饮食对实验性乳腺癌的发生有明显的刺激作用,表明这种脂质在乳腺肿瘤发生的起始和促进中发挥着作用。此外,结果表明橄榄油可以作为实验性乳腺癌的负调节剂。另一方面,通过化学发光Northern印迹在乳腺癌中检测到两种EGFR转录物和一种neu mRNA。数据分析表明,高脂肪玉米油饮食有降低 EGFR 2.7 kb mRNA 的趋势,该 EGFR 编码一种截短形式的受体,没有酶活性。高脂橄榄油饮食增加了EGFR mRNA水平,特别是2.7 kb以上的mRNA水平,并降低了neu mRNA的相对丰度。这些数据表明,膳食脂质对乳腺癌发生的调节作用可能导致EGFR和neu mRNA的变化,导致高脂玉米油饮食增加EGFR活性,而高脂橄榄油饮食减少EGFR和Neu信号转导通路。
In this study we have investigated the influence of dietary mono- and polyunsaturated lipids on 7,12-dimethylbenz(alpha)anthracene (DMBA)-induced mammary tumorigenesis, and the modulation of expression of c-erbB1/EGFR and c-erbB2/neu as a mechanism of this influence. Two series of Sprague-Dawley rats were given a single dose of DMBA. Animals from Series 1 were fed a semi-synthetic low-fat or high-fat corn oil diet, following an initiation-promotion experimental design. Rats from Series 2 were fed low-fat or different high-fat diets (rich in corn oil or rich in olive oil) in the promotion stage of mammary carcinogenesis. High corn oil diet showed clearly a stimulatory effect on experimental breast carcinogenesis, suggesting a role of this kind of lipids on initiation and promotion of mammary tumorigenesis. Moreover, results suggested that olive oil acts as a negative modulator of the experimental breast cancer. On the other hand, two transcripts of EGFR and one neu mRNA were detected by chemiluminescent Northern blot in mammary adenocarcinomas. Analysis of data showed the tendency that high-fat corn oil diet decreases the 2.7 kb mRNA of EGFR, encoding a truncated form of the receptor with no enzimatic activity. High-fat olive oil diet increased EGFR mRNA levels, specially those from 2.7 kb, and decreased the relative abundance of neu mRNA. These data suggest that the modulating effect of dietary lipids on mammary carcinogenesis could result in changes of EGFR and neu mRNA, leading to an increase of EGFR activity by high-fat corn oil diet and a decrease of EGFR and Neu signal transduction pathway by high-fat olive oil diet.