KAI1, a putative marker for metastatic potential in human breast cancer

Abstract

The KAI1 gene maps to chromosome 11p11.2, is a metastasis-suppressor gene for human prostate cancer and also is involved in the progression of human pancreatic and non-small cell lung cancer. Recently, we showed that introduction of a single copy of normal, neomycin-tagged human chromosome 11 into highly metastatic MDA-MB-435 breast cancer cells suppressed breast cancer metastasis. Concomitantly, KAI1 levels were higher in chromosome 11/MDA-MB-435 cell clones. The purpose of this study was to test whether KAI1 expression is indicative of breast cancer metastasis using a panel of immortalized breast epithelial and breast cancer cell lines that represent multiple stages of breast cancer progression. Metastatic cell clones isolated from the parental mixed, wild-type population of MDA-MB-435 cells expressed the lowest levels of KAI1 mRNA and chromosome 11 containing MDA-MB-435 (neol1/MDA-MB-435.A3 and neol1/MDA-MB-435.B1) cells had approximately twice as much KAI1 mRNA than the parental clones. MCF-10A, an immortalized normal-like non-tumorigenic mammary epithelial cell line, had the highest level of KAI1 mRNA. We compared the metastatic propensity and invasive ability of a continuum of breast cancer cells with varying degrees of progression toward malignancy and found that these parameters tended to correlate inversely with KAI1 mRNA expression. These data suggest that, in addition to its role in human prostate, pancreatic and non-small cell lung cancer, KAI1 may also be a useful marker for staging human breast disease.