A gene encoding a protein related to the serpin family of protease inh
ibitors was identified as a candidate tumor suppressor gene that may p
lay a role in human breast cancer. The gene product, called maspin, is
expressed in normal mammary epithelial cells but not in most mammary
carcinoma cell lines. Transfection of MDA-MB-435 mammary carcinoma cel
ls with the maspin gene did not alter the cells' growth properties in
vitro, but reduced the cells' ability to induce tumors and metastasize
in nude mice and to invade through a basement membrane matrix in vitr
o. Analysis of human breast cancer specimens revealed that loss of mas
pin expression occurred most frequently in advanced cancers. These res
ults support the hypothesis that maspin functions as a tumor suppresso
r.