Maspin is a unique member of the serpin family, which functions as a class
II tumor suppressor gene. Despite its known activity against tumor invasion
and motility, little is known about maspin's functions in normal mammary g
land development. In this paper, we show that maspin does not act as a tPA
inhibitor in the mammary gland. However, targeted expression of maspin by t
he whey acidic protein gene promoter inhibits the development of lobular-al
veolar structures during pregnancy and disrupts mammary gland differentiati
on. Apoptosis was increased in alveolar cells from transgenic mammary gland
s at midpregnancy. However, the rate of proliferation was increased in earl
y lactating glands to compensate for the retarded development during pregna
ncy. These findings demonstrate that maspin plays an important role in mamm
ary development and that its effect is stage dependent. (C) 1999 Academic P
ress.