Reduced mammary tumor progression in WAP-TAg/WAP-maspin bitransgenic mice

Maspin is a unique serpin involved in the suppression of tumor growth and m etastasis. To investigate whether increased levels of maspin protect agains t tumor progression in vivo, we established a transgenic model in which mas pin is targeted to mammary epithelial cells by the Whey Acidic Protein (WAP ) promoter for overexpression. We crossed these WAP-maspin transgenic mice with the WAP-TAg mouse model of tumor progression. Maspin overexpression in creased the rate of apoptosis of both preneoplastic and carcinomatous mamma ry epithelial cells. Maspin reduced tumor growth through a combination of r educed angiogenesis and increased apoptosis, The number of pulmonary metast ases was reduced in the presence of maspin overexpression, These data demon strate that targeted overexpression of maspin can inhibit tumor progression in vivo, likely through a combination of increased apoptosis, decreased an giogenesis, and inhibition of tumor cell migration.