Tumour-stromal interactions: Transforming growth factor-β isoforms and hepatocyte growth factor/scatter factor in mammary gland ductal morphogenesis

Table 1 Genetic analysis of TGF-β and HGF/SF function in the mammary gland

Experimental design	Cell type expression^*/tissue affected^†	Phenotype	Reference
Gain of function
MMTV-TGF-β₁	Mammary epithelium	Inhibition of ductal development	[15]
WAP-TGF-β₁	Lobuloalveolar progenitors and cells	Inhibition of alveolar development;	[17]
		aging of stem cells
β-lactoglobulin- TGF-β₃	Alveolar and ductal epithelial cells during	Induction of apoptosis	[12]
	lactation
Retroviral HGF	Primary mammary epithelial cells	Increased TEB number and branching	[32]
	transplanted into the mammary fat pad
Loss of function
MMTV-dnTGF-β receptor II	Mammary epithelium	Precocious lobuloalveolar development	[18]
		and milk production
MMTV-dnTGF-β receptor II	Mammary stroma	Increased lateral branching	[13]
TGF-β₁^-/- SCID	Whole animal	Hypoplastic ductal tree	Ingram W, Robertson SA,
			personal communication
TGF-β₁^+/- p21^--/--	Whole animal	Accelerated mammary development;	[10]
		normal adult structure
SMAD-3^--/--	Whole animal	Hypoplastic mammary epithelium	[21]
TGF-β₃^--/--	Mammary epithelium into wild-type stroma	Reduced apoptosis during involution.	[12]
		Normal mammary development
dnMet	Mammary tumor cells in culture followed	Increased tubule formation	[30]
	by transplantation to mice

^*For gain of function. ^†For loss of function. dn, dominant negative. MMTV, mouse mammary tumor virus; WAP = whey acidic protein.

ISSN: 1465-542X