EFFECT OF MTS1 (S100A4) EXPRESSION ON THE PROGRESSION OF HUMAN BREAST-CANCER CELLS

The mtsI (SI00A4) gene, encoding a Ca2+-binding protein of the S-I00 s ubfamily, is involved in the control of tumor metastasis in some murin e tumor cell lines. To further analyze its role, we transfected hormon e-responsive human breast cancer MCF-7 cells with the mts I gene under the control of a strong constitutive promoter. All of the 3 tested cl ones (MCF-7/mtsI) producing Mtsl protein acquired an ability for hormo ne-independent growth in nude mice. Tumors derived from mts I transfec tants revealed local invasiveness into surrounding muscle and adipose tissues and metastasized to regional lymph nodes and lungs, characteri stics which are rarely observed with parental MCF-7 cells. Electron-mi croscopic analysis of MCF-7/mtsI cells demonstrated structural changes in anchoring junctions, particularly in intermediate filament attachm ent sites (desmosomes). The mtsI-transfected clones expressed estrogen receptor, and their growth in tissue culture was both estrogen- and a nti-estrogen-responsive. Changes in regulation of the estrogen-depende nt proteins progesterone receptor and cathepsin D were observed in som e of the transfected clones. Our results indicate that mtsI expression in human breast cancer cells inducer several changes characteristic o f malignant phenotype and tumor progression.