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.
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