CORRELATION BETWEEN REDUCTION OF METASTASIS IN THE MDA-MB-435 MODEL SYSTEM AND INCREASED EXPRESSION OF THE KAI-1 PROTEIN

Using microcell-mediated transfer of a normal chromosome 11 into the h ighly metastatic MDA-MB-435 human breast carcinoma cell line, we previ ously showed that human chromosome 11 contains a metastasis-suppressor gene for breast cancer. A known metastasis-suppressor gene, kai-1, an d a related family member, tapa-1, have been mapped to chromosome 11p1 1.2 and 11p15.5, respectively. To determine if these genes are respons ible for the metastasis suppression seen in our microcell hybrids, we examined their expression by western blot analysis. Although tapa-l ex pression did not significantly correlate with metastasis suppression, kai-1 production was dramatically increased in the metastasis-suppress ed chromosome 11 microcell hybrids and unchanged in the metastatic chr omosome 6 controls. Transfection of full-length kai-1 cDNA into MDA-MB -435 cells resulted in clones that did not have a significantly decrea sed in vivo incidence of lung metastases. However, western blot analys is showed that the primary tumors and the metastatic lesions of the tr ansfectants had decreased levels of kai-1 protein compared with the in oculated cells. Furthermore, several of the transfectant clones expres sed heavily modified kai-1 protein compared with that of the microcell hybrids. Our data indicate that protein modification may affect the n ormal function of kai-1 in vivo and that a threshold level of kai-1 pr otein expression may be necessary for suppression of the metastatic ph enotype. (C) 1998 Wiley-Liss, Inc.