title: Progesterone receptor isoform A may regulate the effects of neoadjuvant aglepristone in canine mammary carcinoma.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  These findings suggest that the antiproliferative effects of aglepristone in canine mammary carcinomas are mediated by progesterone receptor isoform A.
authors.affiliation: 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. v22gulus@uco.es.
authors.forename: Silvia
authors.initials: S
authors.lastname: Guil-Luna
authors.affiliation: Institute of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. stenvang@life.ku.dk.
authors.forename: Jan
authors.initials: J
authors.lastname: Stenvang
authors.affiliation: Institute of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. nbr@life.ku.dk.
authors.forename: Nils
authors.initials: N
authors.lastname: Brünner
authors.affiliation: Small Animal Clinic Thor, Córdoba, Spain. cvthor@cvthor.com.
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: De Andrés
authors.affiliation: Small Animal Clinic Canymar, Cádiz, Spain. canymar@gmail.com.
authors.forename: Eva
authors.initials: E
authors.lastname: Rollón
authors.affiliation: Small Animal Clinic Recuerda, Granada, Spain. victor.domingo@gmail.com.
authors.forename: Víctor
authors.initials: V
authors.lastname: Domingo
authors.affiliation: 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. v32sacer@uco.es.
authors.forename: Raquel
authors.initials: R
authors.lastname: Sánchez-Céspedes
authors.affiliation: 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. an2mirum@uco.es.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Millán
authors.affiliation: 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. an1magoj@uco.es.
authors.forename: Juana
authors.initials: J
authors.lastname: Martín de Las Mulas
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D004283:Dog Diseases / Q000188:drug therapy* / Q000503:physiopathology; D004285:Dogs; D004963:Estrenes / Q000627:therapeutic use*; D005260:Female; D015674:Mammary Neoplasms, Animal / Q000188:drug therapy* / Q000503:physiopathology; D020360:Neoadjuvant Therapy / Q000379:methods / Q000662:veterinary*; D016133:Polymerase Chain Reaction / Q000662:veterinary; D011980:Receptors, Progesterone / Q000378:metabolism / Q000502:physiology*
chemical_list: D004963:Estrenes; D011980:Receptors, Progesterone; C101118:progesterone receptor A; C097314:progesterone receptor B; C419063:aglepristone