Induction of the transferrin receptor gene by benzo[a]pyrene in breast cancer MCF-7 cells: Potential as a biomarker of PAH exposure

Michael Q. Kemp, Wenjing Liu, Patricia A. Thorne, Michael D. Kane, Ornella Selmin, Donato Romagnolo

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental DNA-damaging agents regarded as risk factors for human disease, including lung and breast cancer. The biotransformation of PAHs to carcinogenic metabolites is mediated by the aromatic hydrocarbon receptor (AhR), which activates transcription at xenobiotic responsive elements (XREs = 5′-GCGTG-3′) found in the promoter regions of genes encoding for detoxifying enzymes, including CYP1A1 and CYP1B1. In this study, we wished to identify novel biomarkers that may be useful in monitoring critical carcinogenic events of the breast induced by PAHs. Using a GeneMAP™ CancerArray, we analyzed in breast cancer MCF-7 cells the temporal effects of the AhR agonist benzo[a]pyrene (B[a]P), which is a prototype PAH and known environmental carcinogen. Genes upregulated at least threefold by B[a]P and containing potential XREs within their promoter regions included CYP1A1, CYP1B1, paired box gene 3 (PAX3), cortactin (CTTN/EMS1), β-2-microglobulin [B2M], and transferrin receptor (TfR]. The stimulatory effects of B[a]P on expression of these genes were abrogated by cotreatment with the AhR antagonist flavonoid, α- napthoflavone (ANF). The TfR gene was selected for further analysis as its promoter region contains two potential XREs and its expression has been shown to be increased in breast cancer cells. Accumulation of TfR mRNA in B[a]P-treated cells was confirmed by quantitative real time PCR. Transient transfection studies indicated that the transcriptional activity of the TfR promoter was stimulated by B[a]P, whereas ANF counteracted this induction. These results indicate that the TfR gene may be a potential biomarker of PAH exposure.

Original languageEnglish (US)
Pages (from-to)518-526
Number of pages9
JournalEnvironmental and Molecular Mutagenesis
Volume47
Issue number7
DOIs
StatePublished - Aug 2006

Fingerprint

Transferrin Receptors
Benzo(a)pyrene
Polycyclic Aromatic Hydrocarbons
MCF-7 Cells
Biomarkers
pyrene
biomarker
cancer
PAH
Aromatic Hydrocarbons
Genes
Breast Neoplasms
Genetic Promoter Regions
gene
aromatic hydrocarbon
Cytochrome P-450 CYP1A1
Flavonoids
Cortactin
Cells
Environmental Carcinogens

Keywords

  • Aromatic hydrocarbon receptor
  • Benzo[a]pyrene
  • Breast cancer
  • Polycyclic aromatic hydrocarbons
  • Transferrin receptor

ASJC Scopus subject areas

  • Environmental Science(all)
  • Environmental Chemistry
  • Genetics
  • Genetics(clinical)
  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Induction of the transferrin receptor gene by benzo[a]pyrene in breast cancer MCF-7 cells : Potential as a biomarker of PAH exposure. / Kemp, Michael Q.; Liu, Wenjing; Thorne, Patricia A.; Kane, Michael D.; Selmin, Ornella; Romagnolo, Donato.

In: Environmental and Molecular Mutagenesis, Vol. 47, No. 7, 08.2006, p. 518-526.

Research output: Contribution to journalArticle

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abstract = "Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental DNA-damaging agents regarded as risk factors for human disease, including lung and breast cancer. The biotransformation of PAHs to carcinogenic metabolites is mediated by the aromatic hydrocarbon receptor (AhR), which activates transcription at xenobiotic responsive elements (XREs = 5′-GCGTG-3′) found in the promoter regions of genes encoding for detoxifying enzymes, including CYP1A1 and CYP1B1. In this study, we wished to identify novel biomarkers that may be useful in monitoring critical carcinogenic events of the breast induced by PAHs. Using a GeneMAP™ CancerArray, we analyzed in breast cancer MCF-7 cells the temporal effects of the AhR agonist benzo[a]pyrene (B[a]P), which is a prototype PAH and known environmental carcinogen. Genes upregulated at least threefold by B[a]P and containing potential XREs within their promoter regions included CYP1A1, CYP1B1, paired box gene 3 (PAX3), cortactin (CTTN/EMS1), β-2-microglobulin [B2M], and transferrin receptor (TfR]. The stimulatory effects of B[a]P on expression of these genes were abrogated by cotreatment with the AhR antagonist flavonoid, α- napthoflavone (ANF). The TfR gene was selected for further analysis as its promoter region contains two potential XREs and its expression has been shown to be increased in breast cancer cells. Accumulation of TfR mRNA in B[a]P-treated cells was confirmed by quantitative real time PCR. Transient transfection studies indicated that the transcriptional activity of the TfR promoter was stimulated by B[a]P, whereas ANF counteracted this induction. These results indicate that the TfR gene may be a potential biomarker of PAH exposure.",
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