Marginal activity of progesterone receptor B (PR-B) in dogs but high incidence of mammary cancer.

Abstract

Progesterone plays an important role in the normal development and carcinogenesis of the mammary gland. In vitro studies have shown that the canine progesterone receptor B (cPR-B), which is essential for mammary development in the mouse, does not transactivate reporter constructs containing progesterone response elements. Therefore, the question was raised whether the cPR-B was completely devoid of transactivation potential of endogenous progesterone regulated genes. Canine mammary cell lines expressing doxycycline-inducible cPR-B, human PR-B or a chimera in which the canine B-upstream segment (BUS) was replaced by a human BUS were treated for 24h with doxycycline, progesterone or a combination of the two. The expression profiling was subsequently performed using a dog-specific microarray and miRNA primers. Incubation of stably transfected cell lines with doxycycline or progesterone alone, did not change expression of any endogenous gene. Expression of activated human PR-B or the chimera of human BUS with the canine PR resulted in differential expression of >500 genes whereas the activated cPR-B regulated only a subset of 40 genes and to a limited extent. The relevance of the marginal transactivation potential or the consequence of a lack of cPR-B function for the carcinogenesis of mammary gland tumors is discussed.

• Authors: Ana Gracanin, Fabiana A Voorwald, Monique van Wolferen, Elpetra Timmermans-Sprang, Jan A Mol
• Journal: The Journal of steroid biochemistry and molecular biology (J Steroid Biochem Mol Biol) Vol. 144 Pt B Pg. 492-9 (Oct 2014) ISSN: 1879-1220 [Electronic] England
• PMID: 25158022 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• Receptors, Progesterone
• progesterone receptor A
• progesterone receptor B
• Progesterone
• Doxycycline

Topics

• Animals
• Cell Line, Tumor
• Dogs
• Doxycycline (pharmacology)
• Gene Expression Profiling
• Humans
• Incidence
• Mammary Neoplasms, Animal (genetics)
• Progesterone (pharmacology)
• Receptors, Progesterone (genetics)
• Transcriptional Activation