KAI1 protein is down-regulated during the progression of human breast cancer

The KAI1 gene was identified as a metastasis suppressor gene for human pros tate cancer. Recently, we showed that KAI1 mRNA levels were higher in an im mortal, normal-like breast epithelial cell line and nonmetastatic breast ca ncer cell lines but lower substantially in highly metastatic breast cancer cell lines. In this study, we examined KAI1 protein expression in breast ca ncer cell lines by Western blot and immunohistochemical study, KAI1 protein levels paralleled KAI1 mRNA levels and were inversely correlated with the metastatic potential of breast cancer cells. Furthermore, we examined KAI1 protein expression immunohistochemically in specimens from 81 patients with breast cancer and then correlated the findings with the clinical and histo pathological parameters of the patients. High levels of KAI1 protein expres sion were found in normal breast tissues and noninvasive breast cancer (duc tal carcinoma in situ). In contrast, KAI1 expression was reduced in most of the infiltrating breast tumors. We found that, in general, more malignant tumors demonstrated significantly lower KAI1 expression (P = 0.004). Additi onally, among 29 specimens demonstrating multiple stages of malignancy with in a single specimen, 23 demonstrated significant differences in KAI1 expre ssion between benign breast tissue, ductal carcinoma in situ, and invasive carcinoma. The higher the incidence for malignancy within a given specimen, the lower the KAI1 expression (P < 0.001). These data suggest that in adva nced breast cancer, KAI1 expression is down-regulated. Therefore, KAI1 may be a potentially useful indicator of human breast cancer progression.