Key signaling nodes in mammary gland development and cancer: β-catenin

Incassati, Angela; Chandramouli, Anupama; Eelkema, Rachel; Cowin, Pamela

doi:10.1186/bcr2723

Breast Cancer Research

Table 1 Mouse models used to study canonical Wnt signaling in mammary development and cancer

From: Key signaling nodes in mammary gland development and cancer: β-catenin

Mouse model	Structural modification	Mammary phenotype	References
MMTV-ΔN89-β-catenin	Stabilizing deletion of first 89 amino acids of β-catenin Luminal expression	Expansion K18⁺CD29^hi 49f^lo Precocious alveologenesis Adenocarcinoma	[67, 75]
MMTV-ΔN90-β-catenin	Stabilizing deletion of first 90 amino acids of β-catenin Luminal expression	Hyperplasia Adenocarcinoma	[90]
Catnb+/lox(ex3);WAP-Cre	Stabilizing deletion of Exon 3 (codons 5 to 80) of β-catenin	Squamous metaplasia	[93]
Catnb+/lox(ex3);MMTV-Cre	Luminal expression
MMTV-ΔN90-β-catenin x p53^+/-	Stabilizing deletion of β-catenin on a p53 heterozygous background	Adenocarcinomas	[175]
	Luminal expression	Metastases
K5-ΔN57-β-catenin	Stabilizing deletion of first 57 amino acids of β-catenin Basal expression	Precocious development during pregnancy Hyperbranching Multiparous mice develop invasive basal-type carcinoma	[38, 74]
MMTV-Wnt1	Wnt1 expression in luminal epithelia	Expansion of K14⁺, cd24⁺, cd29/49f^hi basal stem cells Hyperbranching Adenocarcinoma	[33, 67, 84, 85]
MMTV-Wnt10b	Expression of long isoform of Wnt10b in luminal epithelia	Precocious alveologenesis Hyperbranching Adenocarcinoma	[61]
MMTV-Lrp6	Expression of Lrp6 in luminal epithelia	Hyperplasia no tumors	[88]
Apc^Min/+	Truncating mutation of APC at codon 850	Focal alveolar hyperplasias Mammary carcinomas (7 to 20% depending on strain background)	[178]
Apc^+/1572	Truncating mutation of APC at codon 1572	Multifocal mammary adenocarcinomas (85.7%) Pulmonary metastases	[95]
K14-cre-Apc^580/+	Truncating mutation of APC at codon 580 Basal expression	Mammary adenocarcinomas	[94]
BLG-Cre; Apc^580S/580S	Truncating mutation of APC at codon 580 Luminal expression	Delayed ductal morphogenesis Metaplasia	[179]
MMTV-rtTA;TRE2-myc- tagged Axin-(IRES) GFP	Doxycycline-inducible Axin in luminal epithelia	Loss of alveologenesis	[76]
WAP-β-engrailed	β-engrailed expressed luminally	Failure to maintain alveoli	[77]
MMTV-β-engrailed		Lactation defect
Lrp5^-/-	Loss of Lrp5	Loss of placodes Mild ductal hypoplasia Reduced regenerative capacity Resistant to Wnt-induced tumorigenesis	[34, 39]
Lrp6^-/-	Loss of Lrp6	Impaired sprouting, placode and fat pad development Decreased number of TEBs in heterozygotes	[40]
Wnt4^-/-	Loss of Wnt4	Delayed side-branching	[69]
Wnt5a^-/-	Loss of Wnt5a	Accelerated ductal morphogenesis	[64]
K5-rtTA/tetO-DKK1	Ectopic expression of Dkk1	Loss of mammary line and all placodal development	[36]
K14-Cre/Pygo2 flox	Loss of Pygo2 in mammary epithelium	Loss and small placodes Progressive loss of progenitor cell population	[38]
Pin1^-/-	Loss of Pin1	Severe decrease in ductal and alveolar development during pregnancy	[80]
RANK^-/-	Loss of RANK receptor	Loss of alveologenesis Failure to lactate Impaired side-branching in transplanted null outgrowths	[78, 79]
Lef1^-/-	Loss of Lef1	Impaired placodes Impaired bud morphogenesis	[37]
Rspo^-/-	Loss of Rspo1	Defective side branching	[73]

APC, adenomatous polyposis coli; DKK, Dickkopf; GFP, green fluorescence protein; LRP, low-density lipoprotein-related protein; MMTV, mouse mammary tumor virus; Pygo2, pygopus homolog 2; RANK, receptor activator of NF-κB; TEB, terminal end bud; WAP, whey acidic protein.

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ISSN: 1465-542X

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