Mohibi Shakur, Mirza Sameer, Band Hamid, Band Vimla
Department of Genetics, Cell Biology, and Anatomy, College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska.
J Carcinog. 2011;10:35. doi: 10.4103/1477-3163.91116. Epub 2011 Dec 22.
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.
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。