The process of malignant progression in human breast cancer.
Malignant progression in breast cancer represents the processes through which localized, hormone-dependent tumor cells become resistant to endocrine manipulations and metastasize to sites distant from the primary tumor. By selection in ovariectomized athymic nude mice, we have isolated a variant (MIII) of the hormone-dependent, poorly invasive, human breast cancer cell line MCF-7. MIII cells have lost their absolute requirement for estrogen to form proliferating tumors in nude mice. Furthermore, these tumors are significantly more invasive than the parental MCF-7 cell line. MIII cells retain some responsivity to estrogens and antiestrogens, indicating that they have progressed to a hormone-independent but hormone-esponsive phenotype. In an attempt to determine the nature of this process, we have compared the phenotype of MIII cells with that of other MCF-7 variants. These comparisons strongly suggest that the factors contributing to perturbations in antiestrogen sensitivity, hormone-dependent growth, metastatic potential and tumorigenicity are essentially independent of each other and acquired in a random manner. Loss of estrogen receptor expression and overexpression of EGF receptors tend to occur later in the process of malignant progression.
Clarke
R
R
Vincent T. Lombardi Cancer Research Center, Georgetown University Medical Center, Washington.
Dickson
R B
RB
Brünner
N
N
D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology / Q000503:physiopathology*; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D004967:Estrogens / Q000502:physiology; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D010641:Phenotype; D014407:Tumor Cells, Cultured
D004967:Estrogens