Isolation and characterization of variant benzo[a]pyrene‐resistant T47D human breast‐cancer cells

Abstract

T47D human breast cancer cells were grown in I μM benzo[a]pyrene (BaP) for 3.5 months, and 2 BaP-resistant (BaPR) variant cell lines (C5 and C10) were isolated. Decreased aryl hydrocarbon (Ah)-responsiveness in the C5 and C10 BaPR cells was characterized by lower (80 to 90%) induction of CYPIAI-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. 17β-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. © 1996 Wiley-Liss, Inc.