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雌激素受体阳性乳腺癌的小鼠模型

Mouse models of estrogen receptor-positive breast cancer.

作者信息

Mohibi Shakur, Mirza Sameer, Band Hamid, Band Vimla

机构信息

Department of Genetics, Cell Biology, and Anatomy, College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska.

出版信息

J Carcinog. 2011;10:35. doi: 10.4103/1477-3163.91116. Epub 2011 Dec 22.

Abstract

Breast cancer is the most frequent malignancy and second leading cause of cancer-related deaths among women. Despite advances in genetic and biochemical analyses, the incidence of breast cancer and its associated mortality remain very high. About 60 - 70% of breast cancers are Estrogen Receptor alpha (ER-α) positive and are dependent on estrogen for growth. Selective estrogen receptor modulators (SERMs) have therefore provided an effective targeted therapy to treat ER-α positive breast cancer patients. Unfortunately, development of resistance to endocrine therapy is frequent and leads to cancer recurrence. Our understanding of molecular mechanisms involved in the development of ER-α positive tumors and their resistance to ER antagonists is currently limited due to lack of experimental models of ER-α positive breast cancer. In most mouse models of breast cancer, the tumors that form are typically ER-negative and independent of estrogen for their growth. However, in recent years more attention has been given to develop mouse models that develop different subtypes of breast cancers, including ER-positive tumors. In this review, we discuss the currently available mouse models that develop ER-α positive mammary tumors and their potential use to elucidate the molecular mechanisms of ER-α positive breast cancer development and endocrine resistance.

摘要

乳腺癌是女性中最常见的恶性肿瘤,也是癌症相关死亡的第二大主要原因。尽管在基因和生化分析方面取得了进展,但乳腺癌的发病率及其相关死亡率仍然很高。约60%-70%的乳腺癌为雌激素受体α(ER-α)阳性,其生长依赖雌激素。因此,选择性雌激素受体调节剂(SERM)为治疗ER-α阳性乳腺癌患者提供了一种有效的靶向治疗方法。不幸的是,内分泌治疗耐药性的发生很常见,并导致癌症复发。由于缺乏ER-α阳性乳腺癌的实验模型,我们目前对ER-α阳性肿瘤发生及其对ER拮抗剂耐药所涉及的分子机制的了解有限。在大多数乳腺癌小鼠模型中,形成的肿瘤通常为ER阴性,其生长不依赖雌激素。然而,近年来人们更加关注开发能够产生不同亚型乳腺癌(包括ER阳性肿瘤)的小鼠模型。在这篇综述中,我们讨论了目前可用的能产生ER-α阳性乳腺肿瘤的小鼠模型及其在阐明ER-α阳性乳腺癌发生和内分泌耐药分子机制方面的潜在用途。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8c4/3263010/184b96f8807d/JC-10-35-g001.jpg

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