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.
Luebbe
L
L
Department of Molecular Cytogenetics, Carl Thiem Hospital, Cottbus, Germany.
Schenk
J A
JA
Naundorf
H
H
Karsten
U
U
Wunderlich
V
V
D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology*; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009368:Neoplasm Transplantation; D014407:Tumor Cells, Cultured