TY - JOUR
T1 - Benzo[a]pyrene-resistant MCF-7 human breast cancer cells
T2 - A unique aryl hydrocarbon-nonresponsive clone
AU - Moore, Michael
AU - Wang, Xiahong
AU - Lu, Yu Fang
AU - Wormke, Mark
AU - Craig, Andrew
AU - Gerlach, Jim H.
AU - Burghardt, Robert
AU - Barhoumi, Rola
AU - Safe, Stephen
PY - 1994/4/22
Y1 - 1994/4/22
N2 - Wild-type MCF-7 human breast cancer cells were cultured for 3 months in 1 μM benzo[a]pyrene (BaP), and resistant clones were screened for inducibility of CYP1A1 gene expression by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). One of the BaP-resistant (BaPR) clones exhibited unique genotypic expression which distinguished it from both wild-type and drug-resistant (AdrR) variant MCF-7 cells. Glutathione levels, glutathione S-transferase activities, estrogen receptor levels, estrogen responsiveness, and expression of the multidrug-resistant MDR1 and MRP mRNA levels were similar in the wild-type and BaPR cells, whereas these parameters were reported to be altered in AdrR cells. In contrast, TCDD induced CYP1A1 gene expression and inhibited selected estrogen-induced responses in wild-type but not BaPR MCF-7 cells. Treatment of wild-type and BaP cells with [3H]TCDD resulted in formation of the radio-labeled aryl hydrocarbon (Ah) 6 S nuclear receptor complex in both cell lines. The loss of Ah responsiveness in the BaPR variant cells correlated with the failure of the nuclear or transformed cytosolic Ah receptor complex to bind genomic dioxin-responsive elements as determined in gel retardation assays.
AB - Wild-type MCF-7 human breast cancer cells were cultured for 3 months in 1 μM benzo[a]pyrene (BaP), and resistant clones were screened for inducibility of CYP1A1 gene expression by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). One of the BaP-resistant (BaPR) clones exhibited unique genotypic expression which distinguished it from both wild-type and drug-resistant (AdrR) variant MCF-7 cells. Glutathione levels, glutathione S-transferase activities, estrogen receptor levels, estrogen responsiveness, and expression of the multidrug-resistant MDR1 and MRP mRNA levels were similar in the wild-type and BaPR cells, whereas these parameters were reported to be altered in AdrR cells. In contrast, TCDD induced CYP1A1 gene expression and inhibited selected estrogen-induced responses in wild-type but not BaPR MCF-7 cells. Treatment of wild-type and BaP cells with [3H]TCDD resulted in formation of the radio-labeled aryl hydrocarbon (Ah) 6 S nuclear receptor complex in both cell lines. The loss of Ah responsiveness in the BaPR variant cells correlated with the failure of the nuclear or transformed cytosolic Ah receptor complex to bind genomic dioxin-responsive elements as determined in gel retardation assays.
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M3 - Article
C2 - 7909315
AN - SCOPUS:0028180131
SN - 0021-9258
VL - 269
SP - 11751
EP - 11759
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 16
ER -