ISOLATION AND CHARACTERIZATION OF VARIANT BENZO[A]PYRENE-RESISTANT T47D HUMAN BREAST-CANCER CELLS

T47D human breast cancer cells were grown in I mu M benzo[a]pyrene (Ba P) for 3.5 months, and 2 BaP-resistant (BaPR) variant cell lines (C5 a nd C10) were isolated. Decreased aryl hydrocarbon (Ah)-responsiveness in the C5 and C10 BaPR cells was characterized by lower (80 to 90%) in duction of CYPIAI-dependent activity by 2,3,7,8-teerachlorodibenzo-p-d ioxin (TCDD), lower levels of the nuclear Ah receptor complex and sign ificantly 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. 17 beta-Estrad iol induced proliferation of both wild-type and BaPR T47D cells, and T CDD inhibited this response but did not down-regulate nuclear ER level s. The unique characteristics of the BaPR T47D variant cells will be u sed to further elucidate the mechanism of interaction between the ER a nd Ah receptor signalling pathways. (C) 1996 Wiley-Liss, Inc.