Lanari Claudia, Lamb Caroline A, Fabris Victoria T, Helguero Luisa A, Soldati Rocío, Bottino María Cecilia, Giulianelli Sebastián, Cerliani Juan Pablo, Wargon Victoria, Molinolo Alfredo
Laboratory of Hormonal Carcinogenesis, Instituto de Biología y Medicina Experimental (IBYME)-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), C1428ADN, Buenos Aires, CF, Argentina.
Endocr Relat Cancer. 2009 Jun;16(2):333-50. doi: 10.1677/ERC-08-0244. Epub 2009 Feb 3.
More than 60% of all breast neoplasias are ductal carcinomas expressing estrogen (ER) and progesterone receptors (PR). By contrast, most of the spontaneous, chemically or mouse mammary tumor virus induced tumors, as well as tumors arising in genetically modified mice do not express hormone receptors. We developed a model of breast cancer in which the administration of medroxyprogesterone acetate to BALB/c female mice induces mammary ductal carcinomas with a mean latency of 52 weeks and an incidence of about 80%. These tumors are hormone-dependent (HD), metastatic, express both ER and PR, and are maintained by syngeneic transplants. The model has been further refined to include mammary carcinomas that evolve through different stages of hormone dependence, as well as several hormone-responsive cell lines. In this review, we describe the main features of this tumor model, highlighting the role of PR as a trigger of key signaling pathways mediating tumor growth. In addition, we discuss the relevance of this model in comparison with other presently used breast cancer models pointing out its advantages and limitations and how, this model may be suitable to unravel key questions in breast cancer.
所有乳腺肿瘤中超过60%是表达雌激素(ER)和孕激素受体(PR)的导管癌。相比之下,大多数自发的、化学诱导或小鼠乳腺肿瘤病毒诱导的肿瘤,以及基因改造小鼠中产生的肿瘤均不表达激素受体。我们开发了一种乳腺癌模型,给BALB/c雌性小鼠注射醋酸甲羟孕酮可诱导乳腺导管癌,平均潜伏期为52周,发病率约为80%。这些肿瘤是激素依赖性(HD)的、具有转移性,同时表达ER和PR,并通过同基因移植得以维持。该模型已进一步优化,纳入了经历不同激素依赖阶段演变的乳腺癌,以及几种激素反应性细胞系。在本综述中,我们描述了该肿瘤模型的主要特征,强调了PR作为介导肿瘤生长的关键信号通路触发因素的作用。此外,我们将此模型与目前使用的其他乳腺癌模型进行比较,讨论其相关性,指出其优势和局限性,以及该模型如何可能适合于阐明乳腺癌中的关键问题。