title: 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.affiliation: Department of Clinical Sciences of Companion, Animals Faculty of Veterinary Medicine, Utrecht University, Yalelaan 104, 3584 CM Utrecht, The Netherlands.
authors.forename: Ana
authors.initials: A
authors.lastname: Gracanin
authors.affiliation: FCAV, UNESP - Univ Estadual Paulista, Jaboticabal, SP, Brazil.
authors.forename: Fabiana A
authors.initials: FA
authors.lastname: Voorwald
authors.affiliation: Department of Clinical Sciences of Companion, Animals Faculty of Veterinary Medicine, Utrecht University, Yalelaan 104, 3584 CM Utrecht, The Netherlands.
authors.forename: Monique
authors.initials: M
authors.lastname: van Wolferen
authors.affiliation: Department of Clinical Sciences of Companion, Animals Faculty of Veterinary Medicine, Utrecht University, Yalelaan 104, 3584 CM Utrecht, The Netherlands.
authors.forename: Elpetra
authors.initials: E
authors.lastname: Timmermans-Sprang
authors.affiliation: Department of Clinical Sciences of Companion, Animals Faculty of Veterinary Medicine, Utrecht University, Yalelaan 104, 3584 CM Utrecht, The Netherlands. Electronic address: j.a.mol@uu.nl.
authors.forename: Jan A
authors.initials: JA
authors.lastname: Mol
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004285:Dogs; D004318:Doxycycline / Q000494:pharmacology; D020869:Gene Expression Profiling; D006801:Humans; D015994:Incidence; D015674:Mammary Neoplasms, Animal / Q000235:genetics*; D011374:Progesterone / Q000494:pharmacology; D011980:Receptors, Progesterone / Q000235:genetics*; D015533:Transcriptional Activation
chemical_list: D011980:Receptors, Progesterone; C101118:progesterone receptor A; C097314:progesterone receptor B; D011374:Progesterone; D004318:Doxycycline
keywords: Canine; Mammary cancer; Progesterone-receptor B