Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, 14853, Ithaca, NY, USA.
Department of Veterinary & Animal Sciences, University of Massachusetts, 01003, Amherst, MA, USA.
J Mammary Gland Biol Neoplasia. 2022 Jun;27(2):185-210. doi: 10.1007/s10911-022-09522-w. Epub 2022 Jul 29.
Mammary cancer, or breast cancer in women, is a polygenic disease with a complex etiopathogenesis. While much remains elusive regarding its origin, it is well established that chemical carcinogens and endogenous estrogens contribute significantly to the initiation and progression of this disease. Rats have been useful models to study induced mammary cancer. They develop mammary tumors with comparable histopathology to humans and exhibit differences in resistance or susceptibility to mammary cancer depending on strain. While some rat strains (e.g., Sprague-Dawley) readily form mammary tumors following treatment with the chemical carcinogen, 7,12-dimethylbenz[a]-anthracene (DMBA), other strains (e.g., Copenhagen) are resistant to DMBA-induced mammary carcinogenesis. Genetic linkage in inbred strains has identified strain-specific quantitative trait loci (QTLs) affecting mammary tumors, via mechanisms that act together to promote or attenuate, and include 24 QTLs controlling the outcome of chemical induction, 10 QTLs controlling the outcome of estrogen induction, and 4 QTLs controlling the outcome of irradiation induction. Moreover, and based on shared factors affecting mammary cancer etiopathogenesis between rats and humans, including orthologous risk regions between both species, rats have served as useful models for identifying methods for breast cancer prediction and treatment. These studies in rats, combined with alternative animal models that more closely mimic advanced stages of breast cancer and/or human lifestyles, will further improve our understanding of this complex disease.
乳腺癌，或女性乳腺癌，是一种具有复杂发病机制的多基因疾病。虽然其起源仍有许多未解之谜，但化学致癌物和内源性雌激素对该病的发生和发展有重要贡献已得到充分证实。大鼠是研究诱导性乳腺癌的有用模型。它们的乳腺肿瘤具有与人相似的组织病理学特征，并且根据品系的不同，对乳腺癌的抵抗力或易感性存在差异。虽然一些大鼠品系（例如 Sprague-Dawley）在用化学致癌物 7,12-二甲基苯并[a]蒽（DMBA）处理后很容易形成乳腺肿瘤，但其他品系（例如 Copenhagen）对 DMBA 诱导的乳腺致癌作用具有抗性。近交系中的遗传连锁已经确定了影响乳腺肿瘤的特定品系数量性状基因座（QTL），这些基因座通过共同作用的机制促进或减弱，包括控制化学诱导结果的 24 个 QTL、控制雌激素诱导结果的 10 个 QTL 和控制辐射诱导结果的 4 个 QTL。此外，基于影响大鼠和人类乳腺癌发病机制的共同因素，包括两者之间的同源风险区域，大鼠已被用作识别乳腺癌预测和治疗方法的有用模型。这些在大鼠中的研究，结合更能模拟乳腺癌晚期和/或人类生活方式的替代动物模型，将进一步加深我们对这种复杂疾病的理解。
