Abstract
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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12917-014-0296-2) contains supplementary material, which is available to authorized users.
Highlights
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
Canine progesterone receptor (PR) exists as two isoforms: PR isoform A (PRA) and PR isoform B (PRB), which are transcribed from a single gene under the control of different promoters [4]
A significant decrease in PR mRNA expression was noted after treatment in PR-positive tumours in the aglepristone-treated group alone (p = 0.001) (Table 2), whereas tumours in the control group and PR-negative tumours in the aglepristone-treated group exhibited no significant change
Summary
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. 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. Neoadjuvant treatment with the antiprogestin aglepristone has been found to decrease cell proliferation in PR positive canine mammary carcinomas [3]. Normal human breast tissue expresses both PRA and PRB at equimolar levels [5]. Western blot analysis of normal and tumoural mammary glands from six female dogs (two in metoestrus, two in anoestrus and two after prolonged treatment with progestins) showed that PRA was either equimolar or
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