The biology of breast tumor progression. Acquisition of hormone independence and resistance to cytotoxic drugs.
Many breast tumors appear to follow a predictable clinical pattern, being initially responsive to endocrine therapy and to cytotoxic chemotherapy but ultimately exhibiting a phenotype resistant to both modalities. Using the MCF-7 human breast cancer cell line as an example of an 'early' phenotype (estrogen and progesterone receptor positive, steroid responsive, low metastatic potential), we have isolated and characterized a series of hormone-independent but hormone-responsive variants (MIII and MCF7/LCC1). However, these variants remain responsive to both antiestrogens and cytotoxic drugs (methotrexate and colchicine). MIII and MCF7/LCC1 cells appear to mimic some of the critical aspects of the early progression to a more aggressive phenotype. An examination of the phenotype of these cells suggests that some hormone-independent breast cancer cells are derived from hormone-dependent parental cells. The development of a hormone-independent phenotype can arise independently of acquisition of a cytotoxic drug resistant phenotype.
Leonessa
F
F
Vincent T. Lombardi Cancer Research Center, Georgetown University Medical School, Washington, DC 20007.
Boulay
V
V
Wright
A
A
Thompson
E W
EW
Brünner
N
N
Clarke
R
R
D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D003078:Colchicine / Q000494:pharmacology; D004351:Drug Resistance; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008727:Methotrexate / Q000494:pharmacology; D051379:Mice; D008819:Mice, Nude; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy / Q000503:physiopathology; D010641:Phenotype; D014407:Tumor Cells, Cultured
D003078:Colchicine; D008727:Methotrexate