T47D human breast cancer cells were grown in 1 μM benzo[a]pyrene (BaP) for 3.5 months, and 2 BaP-resistant (BaP(R)) variant cell lines (C5 and C10) were isolated. Decreased aryl hydrocarbon (Ah)-responsiveness in the C5 and C10 BaP(R) cells was characterized by lower (80 to 90%) 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 BaP(R) T47D cells. 17β-Estradiol induced proliferation of bath wild-type and BaP(R) T47D cells, and TCDD inhibited this response but did not down-regulate nuclear ER levels. The unique characteristics of the BaP(R) T47D variant cells will be used to further elucidate the mechanism of interaction between the ER and Ah receptor signalling pathways.
|Original language||English (US)|
|Number of pages||7|
|Journal||International Journal of Cancer|
|State||Published - Mar 28 1996|
ASJC Scopus subject areas
- Cancer Research