O'Leary Kathleen A, Shea Michael P, Schuler Linda A
Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, WI, USA,
Adv Exp Med Biol. 2015;846:201-20. doi: 10.1007/978-3-319-12114-7_9.
Elevated exposure to prolactin (PRL) is epidemiologically associated with an increased risk of aggressive ER+ breast cancer. To understand the underlying mechanisms and crosstalk with other oncogenic factors, we developed the NRL-PRL mouse. In this model, mammary expression of a rat prolactin transgene raises local exposure to PRL without altering estrous cycling. Nulliparous females develop metastatic, histotypically diverse mammary carcinomas independent from ovarian steroids, and most are ER+. These characteristics resemble the human clinical disease, facilitating study of tumorigenesis, and identification of novel preventive and therapeutic approaches.
从流行病学角度来看，催乳素（PRL）暴露增加与侵袭性雌激素受体阳性（ER+）乳腺癌风险升高相关。为了解其潜在机制以及与其他致癌因素的相互作用，我们构建了NRL-PRL小鼠模型。在该模型中，大鼠催乳素转基因在乳腺中的表达增加了局部PRL暴露，而不改变发情周期。未生育的雌性小鼠会发生转移性、组织学类型多样的乳腺癌，且独立于卵巢类固醇，其中大多数为ER+。这些特征与人类临床疾病相似，有助于研究肿瘤发生，并确定新的预防和治疗方法。
