Transforming and oncogenic potential of activated c-Ha-ras in three immortalized human breast epithelial cell lines

The ability of activated c-Ha-ras (codon 12 valine) to transform human breast epithelial cells varied for three different immortalized normal human breast epithelial cell lines established from two different women. Although activated c-Ha-ras may transform and induce a preneoplastic phenotype in MCF10A cells, activated c-Ha-ras was not sufficient to transform MCF10-2A cells. Only two of three MCF10-2A clones which expressed mutant p21 protein acquired the ability to form colonies in soft agar. When xenografted into nude beige mice, two MCF10-2A clones formed squamous carcinomas and one formed no lesions at all. The ability to form tumors did not correlate with growth in soft agar. All three activated c-Ha-ras-transfected clones of MCF-12A formed colonies in soft agar but only two produced squamous carcinomas in nude beige mice. Unlike activated c-Ha-ras-transfected MCF10A cells, none of the activated c-Ha-ras-transfected MCF10-2A or MCF-12A clones formed ducts in xenografts. Rather, initial xenograft lesions consisted of nests of cells with squamous differentiation. These observations illustrate that additional events are involved in the transformation and progression of human breast epithelial cells with activated c-Ha-ras.