Reverse transformation of human mammary carcinoma cells

Exposure of cells derived from human mammary carcinoma cell line, MaTu, to daunorubicin started a selection process which reproducibly gave rise to sublines with different phenotypes. One subline exhibited a fibroblast-like morphology (MaTu/c7), while others retained the epitheloid phenotype of the parental cells (MaTu/p). Among the latter was clone 8 (MaTu/c8) which displayed piling-up structures not seen in MaTu/p cells. Striking differences were detected on immunocytochemistry using the anti-cytokeratin 19 antibody A53-B/A2 which positively reacted with cells from MaTu/c7, but not with those of MaTu/c8 and MaTu/p. In contrast, the anti-blood group H 2 antibody A46-B/B10 positively stained cells from MaTu/c8 and MaTu/p, but not those of MaTu/c7. Assays for tumorigenicity in nude mice demonstrated that MaTu/c7 is far less tumorigenic than MaTu/p, while MaTu/c8 showed a pattern distinguishing it from MaTu/p cells. Cross-resistance assays showed decreasing drug resistance in the order MaTu/c8 > MaTu/c7 > MaTu/p. These data suggest drug-induced differentiation with reversion of the neoplastic phenotype in MaTu/c7 and some form of malignant progression in MaTu/c8. This model system may be helpful for understanding cancer development, especially its relation to differentiation.