ABSTRACT
Maspin (w^mmary serine protease /Vzhibitor) is a 42 kDa protein that shares significant sequence homology with several members of the serpin (serine protease inhibitor) family, including plasminogen activation inhibitors 1 and 2 (PAI-1 and PAI-2), al-antitrypsin , and non-inhibitor proteins such as ovalbumin.1’2 It is expressed in normal human mammary epithelial cells2 and is associated with secretory vesicles and cellular surface.3 It has been shown that maspin associates with tumor suppression activity.1,4 Transfecting human mammary carcinoma cells with the maspin gene reduces tumor induction and metastasis in nude mice and in vitro invasion of basement membrane.2 In primary breast cancer cells, maspin is downregulated and its expression is inhibited in metastasis. It has been suggested that this decrease in maspin expression may be due to the absence of transactivation through the ets and Apl elements in the promoter of maspin gene.5 The expression of maspin can also be repressed by a negative hormonal response element in the prostate cells.6 Therefore, the level of maspin expression in cancer cells may be primarily regulated by a transcriptional control. Interestingly, it has been shown recently that p53 directly upregulates the expression of maspin in breast and prostate cancer cell lines.7 Furthermore, DNA-damaging agents and cytotoxic drugs induce endogenous maspin expression in cancer cells containing wild-type p53, but not in cells containing mutant p53.7 Since expression of maspin inhibits the invasiveness and motility of breast and prostate tumor cells, these results suggest that maspin and p53 may cooperate in the negative regulation of tumor cell invasion and metastasis. However, no clinical data have been reported regarding possible association between the expression level of maspin and the survival rate. It is not clear whether maspin expression could provide any prognostic value for cancer patients.
