Reduced mammary tumor progression in WAP-TAg/WAP-maspin bitransgenic mice.
Maspin is a unique serpin involved in the suppression of tumor growth and metastasis. To investigate whether increased levels of maspin protect against tumor progression in vivo, we established a transgenic model in which maspin 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 increased the rate of apoptosis of both preneoplastic and carcinomatous mammary epithelial cells. Maspin reduced tumor growth through a combination of reduced angiogenesis and increased apoptosis. The number of pulmonary metastases was reduced in the presence of maspin overexpression. These data demonstrate that targeted overexpression of maspin can inhibit tumor progression in vivo, likely through a combination of increased apoptosis, decreased angiogenesis, and inhibition of tumor cell migration.
Zhang
M
M
Department of Molecular & Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Shi
Y
Y
Magit
D
D
Furth
P A
PA
Sager
R
R
D000230:Adenocarcinoma / Q000098:blood supply / Q000235:genetics / Q000473:pathology*; D000818:Animals; D000957:Antigens, Viral, Tumor / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis; D002455:Cell Division; D002465:Cell Movement; D018450:Disease Progression; D018572:Disease-Free Survival; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D015870:Gene Expression; D016147:Genes, Tumor Suppressor; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology / Q000556:secondary; D015674:Mammary Neoplasms, Animal / Q000098:blood supply / Q000235:genetics / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008894:Milk Proteins / Q000235:genetics*; D009389:Neovascularization, Pathologic; D023282:Nuclease Protection Assays; D011230:Precancerous Conditions / Q000098:blood supply / Q000235:genetics / Q000473:pathology; D011401:Promoter Regions, Genetic / Q000235:genetics; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D015843:Serpins / Q000235:genetics / Q000378:metabolism*; D019076:Transgenes / Q000235:genetics
D000957:Antigens, Viral, Tumor; D008894:Milk Proteins; D011506:Proteins; D012333:RNA, Messenger; C085344:SERPIN-B5; D015843:Serpins; C024471:whey acidic proteins