Maspin, a Serpin with Tumor-Suppressing Activity in Human Mammary Epithelial Cells

Abstract

A gene encoding a protein related to the serpin family of protease inhibitors was identified as a candidate tumor suppressor gene that may play 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 cells 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 vitro. Analysis of human breast cancer specimens revealed that loss of maspin expression occurred most frequently in advanced cancers. These results support the hypothesis that maspin functions as a tumor suppressor.

Effects of demethylating agent 5-aza-2′-deoxycytidine and histone deacetylase inhibitor FR901228 on maspin gene expression in oral cancer cell lines

“…Maspin is a Mr 42000 protein that belongs to the serine protease inhibitor (serpin) superfamily and is expressed in the epithelial cells of the airway, breast, skin, and prostate, but not in skin fibroblasts, lymphocytes, bone marrow, or the heart or kidneys [1,2]. It is known to be a potent tumor suppressor that inhibits cell motility, invasion, angiogenesis, and metastasis [3][4][5][6][7][8].…”

“…Accumulative evidence demonstrates that maspin inhibits the progression of prostate and breast tumors at the late stages of invasion and metastasis [1,7,[9][10][11][12]. In several mammary carcinoma cell lines, maspin is undetectable or is expressed at very low levels [1].…”

“…In several mammary carcinoma cell lines, maspin is undetectable or is expressed at very low levels [1]. A loss of maspin expression correlates with increased metastatic potential in breast cancer and other human tumors.…”

“…Maspin-transfected tumor cells tend to have less necrosis, mitogenesis, and neovascularization, which is associated with better prognosis and lower invasiveness [1,9,10,13]. Domann et al [14] and Futscher et al [2] have shown that the silencing of maspin gene expression is inversely correlated with methylation of the promoter.…”

Phenotypic composition of salivary gland tumors: an application of principle component analysis to tissue microarray data

“…14 Transfection of the maspin gene into a mammary carcinoma cell line promoted aggressiveness of the tumor cells through increased tumor growth, invasion and metastasis. 15 Because maspin expression is observed in the myoepithelial cells of the breast, Sternlicht et al 16 suggested that myoepithelial cells play a role as tumor suppressors. Hermeking et al 17 found that 14-3-3s is induced by g-irradiation and by other DNA-damaging agents in a p53-dependent fashion, and that exogenous expression of 14-3-3s causes G2 arrest in the colorectal cancer cell line, HCT116.…”