Abstract
BackgroundBrisken et al (2000) showed that Wnt4 null mammary glands were deficient in early lobuloalveolar mammary outgrowth during pregnancy, and implicated Wnt4 as an effector for the progesterone-induced mammary growth program. Though ectopic Wnt1 signaling is known to be mitogenic and oncogenic, no endogenously expressed Wnt ligands have ever been directly implicated in mammary growth and morphogenesis. Therefore, we generated conditional transgenic mice to test whether Wnt4 can stimulate mammary epithelial cell growth.ResultsWe found that despite pregnancy-associated expression levels of Wnt4, mammary glands did not display the side-branching typical of early pregnancy. Control experiments designed to test the Wnt4 construct in zebrafish reproduced other studies that demonstrated Wnt4-specific phenotypes distinct from Wnt1-induced phenotypes. Indeed, using qPCR-based array analyses, we found that a specific transcriptional target of Wnt4, namely Wnt16, was induced in Wnt4-expressing transgenic glands, to levels equivalent to that of early pregnant glands.ConclusionTaken together, we propose that Wnt4 is necessary, but not sufficient, to induce side-branch development.
Highlights
Brisken et al (2000) showed that Wnt4 null mammary glands were deficient in early lobuloalveolar mammary outgrowth during pregnancy, and implicated Wnt4 as an effector for the progesterone-induced mammary growth program
Since several Wnt family genes are differentially expressed in the virgin, pregnant, and lactating mammary gland, some of them regulated by ovarian hormones, it would not be surprising if these Wnt proteins have other, as yet unidentified functions [6,7]
To test whether Wnt4 and luciferase expression was regulated by doxycycline, the TMILA-Wnt4 plasmid was transfected into reverse tetracycline trans-activator (rtTA)-expressing 293T cells, and lysates tested for luciferase activity and Wnt4 protein level (Fig. 1B)
Summary
Brisken et al (2000) showed that Wnt null mammary glands were deficient in early lobuloalveolar mammary outgrowth during pregnancy, and implicated Wnt as an effector for the progesterone-induced mammary growth program. Though ectopic Wnt signaling is known to be mitogenic and oncogenic, no endogenously expressed Wnt ligands have ever been directly implicated in mammary growth and morphogenesis. Since several Wnt family genes are differentially expressed in the virgin, pregnant, and lactating mammary gland, some of them regulated by ovarian hormones, it would not be surprising if these Wnt proteins have other, as yet unidentified functions [6,7]. Progesterone signaling is predominantly responsible for the growth and differentiation of the lobuloalveolar lineage that is characteristic of early pregnancy [8]. Brisken et al (2000) concluded that Wnt expression was important to side-branching and lobuloalveolar (page number not for citation purposes)
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