Benzo[a]pyrene-resistant MCF-7 human breast cancer cells. A unique aryl hydrocarbon-nonresponsive clone

M. Moore, X. Wang, Y. F. Lu, M. Wormke, A. Craig, J. H. Gerlach, R. Burghardt, R. Barhoumi, S. Safe

Research output: Contribution to journalArticle

53 Scopus citations

Abstract

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 (BaP(R)) clones exhibited unique genotypic expression which distinguished it from both wild-type and drug-resistant (Adr(R)) 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 BaP(R) cells, whereas these parameters were reported to be altered in Adr(R) cells. In contrast, TCDD induced CYP1A1 gene expression and inhibited selected estrogen-induced responses in wild-type but not BaP(R) MCF-7 cells. Treatment of wild-type and BaP(R) 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 BaP(R) 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.

Original languageEnglish (US)
Pages (from-to)11751-11759
Number of pages9
JournalJournal of Biological Chemistry
Volume269
Issue number16
StatePublished - 1994
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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