Isolation and characterization of variant benzo[a]pyrene-resistant T47D human breast-cancer cells.
T47D human breast cancer cells were grown in 1 microM benzo[a]pyrene (BaP) for 3.5 months, and 2 BaP-resistant (BaPr) variant cell lines (CS and C10) were isolated. Decreased aryl hydrocarbon (Ah)-responsiveness in the CS and C1O BaPr cells was characterized by lower (80 to 900/o) induction of CYP1A1-dependent activity by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), lower levels of the nuclear Ah receptor complex and significantly decreased Ah receptor mRNA levels. Nuclear estrogen receptor (ER) binding and ER mRNA levels were similar in wild-type and mutant cell lines, whereas epidermal growth factor receptor mRNA levels were significantly decreased in the variant BaPr T47D cells. 17beta-Estradiol induced proliferation of both wild-type and BaPr T47D cells, and TCDD inhibited this response but did not down-regulate nuclear ER levels. The unique characteristics of the BaPr T47D variant cells will be used to further elucidate the mechanism of interaction between the ER and Ah receptor signalling pathways.
Moore
M
M
Department of Veterinary Physiology, Texas A&M University, College Station, 77843-4466, USA.
Ruh
M
M
Steinberg
M
M
Safe
S
S
D001483:Base Sequence; D001564:Benzo(a)pyrene / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D018736:DNA Adducts / Q000737:chemistry; D017931:DNA Primers / Q000737:chemistry; D004273:DNA, Neoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004351:Drug Resistance; D004790:Enzyme Induction / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D006801:Humans; D008969:Molecular Sequence Data; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D018336:Receptors, Aryl Hydrocarbon / Q000502:physiology; D014407:Tumor Cells, Cultured
D018736:DNA Adducts; D017931:DNA Primers; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D001564:Benzo(a)pyrene; D004958:Estradiol; D003577:Cytochrome P-450 Enzyme System