Transforming growth factor-β and breast cancer: Lessons learned from genetically altered mouse models

Breast Cancer Research

Table 1 Transgenic mouse models designed to address the roles of TGF-βs in the mammary gland

Gain-of-functionmodels
Model	Transgene	Expression pattern	Developmental phenotype	Tumor phenotype	References
MMTV-TGF-β₁ ^S223/225	Constitutively activated form of TGF-β₁	Mammary epithelium	Decreased ductal development in young animals	Inhibition of tumorigenesis induced by chemical carcinogens or oncogenes	[8,11*]
WAP-TGF-β¹ ^S223/225	Constitutively activated form of TGF-β₁	Mammary epithelium, specifically in lobulo alveolar progenitors and fate-committed daughters	Inability to lactate due to decreased maintenance of lobuloalveolar structures	Inhibition of tumorigenesis induced by TGF-β	[7,9*] (Smith G, unpublished data)
Loss-of-function models
MMTV-DNR	Dominant-negative mutant type II TGF-β receptor	Mammary epithelium	Precocious lobuloalveolar development and production of milk proteins in virgins	Increased spontaneous tumorigenesis in aged mice	[27*] (Moses H, unpublished data)
MMTV-DNR	Dominant-negative mutant type II TGF-β receptor	Mammary epithelium	Increased lobuloalveolar development in virgins	Increased tumorigenesis in response to carcinogens	[28**]
MT-DNR	Dominant-negative mutant type II TGF-β receptor	Mammary stroma	Increased ductal branching	Not described	[29*]

DNR, dominant-negative mutant type II transforming growth factor-β receptor; MMTV, mouse mammary tumor virus; WAP, whey acidic protein; MT, metallothionein promoter; TGF, transforming growth factor.

ISSN: 1465-542X