TABLE 1.

Wnt SIGNALING INVOLVED IN ORGANOGENESIS AND/OR TUMORIGENESIS OF MAMMARY GLANDS AND AIRWAY SUBMUCOSAL GLANDS

Signaling Molecule	Function in Wnt Pathway	Functional Evidences	References
Wnt1, Wnt2, Wnt3a, Wnt4, Wnt5a, Wnt5b, Wnt6, Wnt7b, Wnt10b	Ligands	Expression detected during gland morphogenesis. Overexpression of Wnt induces abnormal glandular development and tumorigenesis. Mice deficient for certain Wnt molecules have reduced ductal branching in mammary glands and reduced SMG formation.	(40, 48, 49, 53–55, 57, 58, 63)
Lef-1	Activator	Required for glandular morphogenesis and the mesenchymal–epithelial transition of Wnt signal.	(38–41, 60)
TCF4	Activator	Expression in early SMG buds, in the mammary epithelium and in tumors.	(40, 68)
DKK1	Inhibitor	Overexpression leads to a failure to form mammary placodes.	(61, 62)
LRP5	Coreceptor	Deficiency leads to smaller mammary placodes and a reduction of the primitive ductal tree.	(50)
Axin	Inhibitor	Inducible expression impairs mammary gland development.	(51)
β-Catenin	Modulator	Expression of dominant negative or active β-catenin leads to impaired development or hyperplasia of mammary glands, respectively.	(52, 54)

Definition of abbreviations: Lef-1 = lymphoid enhancer binding factor 1; SMG = submucosal gland.