OUTGROWTH OF BT-474 HUMAN BREAST-CANCER CELLS IN IMMUNE-DEFICIENT MICE - A NEW IN-VIVO MODEL FOR HORMONE-DEPENDENT BREAST-CANCER

The effect of co-inoculation of basement membrane matrix, Matrigel and two human breast cancer cell lines, BT-474 and SK-BR-3, was tested in immune-deficient mice. Both cell lines strongly overexpresss c-ErbB-2 protein, whereas only BT-474 is reported to be oestrogen receptor pos itive. Go-inoculation of Matrigel and BT-474 cells but not of Matrigel and SK-BR-3 cells resulted in tumour formation in bg-nu-xid mice. Oes trogen supplementation greatly enhanced tumorigenicity, but did not se em to be an absolute requirement. In vivo, BT-474 cells grow as a poor ly differentiated adenocarcinoma with a doubling time of 9.4 +/- 1.1 d ays after inoculation into the neck region. A high proliferative activ ity appears to be compensated by a relatively high rate of cell loss, as BT-474 tumours contain many cells with the typical morphology of ap optotic cell death. Wild-type p53, known to participate in the inducti on of apoptosis, is absent from the tumours, whereas Bcl-2, known to i nhibit apoptosis, is expressed at intermediate levels. BT-474 tumours tend to metastasise to the regional lymph nodes and are capable of for ming micrometastatic lesions in the lung. Flow cytometrical analysis o f DNA ploidy demonstrated no change in tumours compared with the cell line. Immunohistochemical and Row cytometrical detection of a number o f hormone and growth factor receptors, transcription factors, cell adh esion molecules and proteins involved in proliferation and cell death demonstrated no major changes in ploidy and phenotype of tumours compa red with the cell line. High expression of the cell-surface molecules c-ErbB-2 and episialin make it a potentially useful model for research in immune therapy.