KAI1, A PUTATIVE MARKER FOR METASTATIC POTENTIAL IN HUMAN BREAST-CANCER

The KAII gene maps to chromosome 11p11.2, is a metastasis-suppressor g ene for human prostate cancer and also is involved in the progression of human pancreatic and non-small cell lung cancer. Recently, we showe d that introduction of a single copy of normal, neomycin-tagged human chromosome 11 into highly metastatic MDA-MB-435 breast cancer cells su ppressed breast cancer metastasis. Concomitantly, KAII levels were hig her in chromosome 11/MDA-MB-435 cell clones. The purpose of this study was to test whether KAII expresssion is indicative of breast cancer m etastasis using a panel of immortalized breast epithelial and breast c ancer cell lines that represent multiple stages of breast cancer progr ession. Meta static cell clones isolated from the parental mixed, wild -type population of MDA-MB-435 cells expressed the lowest levels of KA II mRNA and chromosome II containing MDA-MB-435 (neo11/MDA-MB-435.A3 a nd neoll/MDA-MB-435.B1) cells had approximately twice as much KAII mRN A than the parental clones, MCF-10A, an immortalized normal-like nontu morigenic mammary epithelial cell line, had the highest level of KAII mRNA. We compared the metastatic propensity and invasive ability of a continuum of breast cancer cells with varying degrees of progression t oward malignancy and found that these parameters tended to correlate i nversely with KAII mRNA expression. These data suggest that, in additi on to its role in human prostate, pancreatic and non-small cell lung c ancer, KAII may also be a useful marker for staging human breast disea se. (C) 1997 Elsevier Science Ireland Ltd.