Guil-Luna Silvia, Stenvang Jan, Brünner Nils, De Andrés Francisco Javier, Rollón Eva, Domingo Víctor, Sánchez-Céspedes Raquel, Millán Yolanda, Martín de Las Mulas Juana
Department of Comparative Pathology, Veterinary Faculty, University of Córdoba, Edificio de Sanidad Animal. Campus de Rabanales. Carretera de Madrid-Cádiz Km. 396, 14014, Córdoba, Spain.
Institute of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
BMC Vet Res. 2014 Dec 17;10:296. doi: 10.1186/s12917-014-0296-2.
Progesterone receptors play a key role in the development of canine mammary tumours, and recent research has focussed on their possible value as therapeutic targets using antiprogestins. Cloning and sequencing of the progesterone receptor gene has shown that the receptor has two isoforms, A and B, transcribed from a single gene. Experimental studies in human breast cancer suggest that the differential expression of progesterone receptor isoforms has implications for hormone therapy responsiveness. This study examined the effects of the antiprogestin aglepristone on cell proliferation and mRNA expression of progesterone receptor isoforms A and B in mammary carcinomas in dogs treated with 20 mg/Kg of aglepristone (n = 22) or vehicle (n = 5) twice before surgery.
Formalin-fixed, paraffin-embedded tissue samples taken before and after treatment were used to analyse total progesterone receptor and both isoforms by RT-qPCR and Ki67 antigen labelling. Both total progesterone receptor and isoform A mRNA expression levels decreased after treatment with aglepristone. Furthermore, a significant decrease in the proliferation index (percentage of Ki67-labelled cells) was observed in progesterone-receptor positive and isoform-A positive tumours in aglepristone-treated dogs.
These findings suggest that the antiproliferative effects of aglepristone in canine mammary carcinomas are mediated by progesterone receptor isoform A.
孕激素受体在犬乳腺肿瘤的发生发展中起关键作用，近期研究聚焦于其作为使用抗孕激素进行治疗靶点的潜在价值。孕激素受体基因的克隆和测序表明，该受体有两种异构体，A和B，由单个基因转录而来。对人类乳腺癌的实验研究表明，孕激素受体异构体的差异表达对激素治疗反应性有影响。本研究检测了抗孕激素阿格列司酮对术前两次接受20mg/Kg阿格列司酮（n = 22）或赋形剂（n = 5）治疗的犬乳腺癌细胞增殖以及孕激素受体异构体A和B的mRNA表达的影响。
使用治疗前后采集的福尔马林固定、石蜡包埋组织样本，通过RT-qPCR和Ki67抗原标记分析总孕激素受体和两种异构体。用阿格列司酮治疗后，总孕激素受体和异构体A的mRNA表达水平均下降。此外，在接受阿格列司酮治疗的犬中，孕激素受体阳性和异构体A阳性肿瘤的增殖指数（Ki67标记细胞的百分比）显著下降。
这些发现表明，阿格列司酮在犬乳腺癌中的抗增殖作用是由孕激素受体异构体A介导的。
