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伴有代谢综合征的乳腺癌小鼠模型的特征描述

Characterisation of a Mouse Model of Breast Cancer with Metabolic Syndrome.

作者信息

Buss Linda A, Mandani Anishah, Phillips Elisabeth, Scott Nicola J A, Currie Margaret J, Dachs Gabi U

机构信息

Mackenzie Cancer Research Group, Department of Pathology, University of Otago, Christchurch, New Zealand.

Christchurch Heart Institute, Department of Medicine, University of Otago, Christchurch, New Zealand.

出版信息

In Vivo. 2018 Sep-Oct;32(5):1071-1080. doi: 10.21873/invivo.11348.

Abstract

BACKGROUND/AIM: Patients with breast cancer and metabolic syndrome have poorer outcomes. We aimed to develop and characterise an apolipoprotein E-null/aromatase knockout (ApoE/ArKO) mouse model of breast cancer with metabolic syndrome to aid research of the mechanisms behind poor prognosis.

MATERIALS AND METHODS

Wild-type, ApoE and ApoE/ArKO mice were orthotopically implanted with EO771 murine breast cancer cells. Tumour growth was monitored and tumours investigated for pathological features such as cancer-associated adipocytes, hypoxia and cancer cell proliferation.

RESULTS

Tumours from ApoE/ArKO mice were significantly more proliferative than those from wild-type mice (p=0.003), and exhibited reduced expression of insulin-like growth factor binding protein-5 (p=0.002). However, ApoE/ArKO mice also had a reduced rate of metastasis compared to wild-type and ApoE mice. Tumour hypoxia and the number of cancer-associated adipocytes did not differ.

CONCLUSION

The ApoE/ArKO model with EO771 breast cancer provides a novel mouse model to investigate the effects of metabolic syndrome on aspects of breast tumour biology.

摘要

背景/目的:患有乳腺癌和代谢综合征的患者预后较差。我们旨在建立并表征一种患有代谢综合征的载脂蛋白E基因敲除/芳香化酶基因敲除(ApoE/ArKO)乳腺癌小鼠模型,以辅助研究预后不良背后的机制。

材料与方法

将EO771小鼠乳腺癌细胞原位植入野生型、ApoE和ApoE/ArKO小鼠体内。监测肿瘤生长情况,并对肿瘤进行病理特征研究,如癌症相关脂肪细胞、缺氧和癌细胞增殖情况。

结果

ApoE/ArKO小鼠的肿瘤增殖明显高于野生型小鼠(p=0.003),且胰岛素样生长因子结合蛋白-5的表达降低(p=0.002)。然而,与野生型和ApoE小鼠相比,ApoE/ArKO小鼠的转移率也较低。肿瘤缺氧情况和癌症相关脂肪细胞的数量没有差异。

结论

携带EO771乳腺癌的ApoE/ArKO模型为研究代谢综合征对乳腺肿瘤生物学各方面的影响提供了一种新型小鼠模型。

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