Researchers in Section of Pharmacotherapy – University of Copenhagen

Progesterone receptor isoform A may regulate the effects of neoadjuvant aglepristone in canine mammary carcinoma

Research output: Contribution to journalJournal articleResearchpeer-review

Silvia Guil-Luna, Jan Stenvang, Nils Brünner, Francisco Javier De Andrés, Eva Rollón, Víctor Domingo, Raquel Sánchez-Céspedes, Yolanda Millán, Juana Martín de las Mulas

BackgroundProgesterone 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.ResultsFormalin-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.ConclusionsThese findings suggest that the antiproliferative effects of aglepristone in canine mammary carcinomas are mediated by progesterone receptor isoform A.

Original languageEnglish
Article number296
JournalB M C Veterinary Research
Volume10
Number of pages8
ISSN1746-6148
DOIs
Publication statusPublished - 2014

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