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Breast Cancer Research and Treatment

, Volume 161, Issue 3, pp 399–407 | Cite as

Aryl hydrocarbon receptor induced intratumoral aromatase in breast cancer

  • Ryoko SaitoEmail author
  • Yasuhiro Miki
  • Shuko Hata
  • Takanori Ishida
  • Takashi Suzuki
  • Noriaki Ohuchi
  • Hironobu Sasano
Preclinical Study

Abstract

Purpose

Aryl hydrocarbon receptor (AhR) inhibits estrogen receptor (ER) pathway, which may suppress estrogen-dependent cell proliferation. However, the correlation between AhR stimulation and intratumoral estrogen synthesis, especially through aromatase, has not been reported to date. In the present study, we examined this correlation in breast cancer cells.

Methods

We examined AhR and aromatase immunoreactivity in 29 patients with invasive ductal carcinoma. We performed in vitro studies using three breast carcinoma cell lines, MCF-7, T47D, and MDA-MB-231.

Results

AhR stimulation induced the mRNA expression of the aromatase gene in vitro in three breast carcinoma cell lines, and increased estrogen synthesis in MCF-7 cell line. Results of microarray analysis showed that AhR-induced aromatase expression was associated with BRCA1 induction. Analysis of patients with breast cancer showed a significant positive correlation between intratumoral AhR and aromatase status. We also compared the effects of AhR stimulation on the induction of intratumoral estrogen synthesis and inhibition of the ER signaling pathway, because AhR exerts contradictory effects on estrogen action in breast carcinoma cells. AhR-induced aromatase expression persisted for a significantly longer duration than AhR-induced ER pathway inhibition. Moreover, breast carcinoma cells treated with an AhR agonist tended to show earlier cell proliferation after removing the agonist than cells not treated with the AhR agonist.

Conclusion

The results of the present study suggest that AhR stimulates estrogen-dependent progression of breast carcinoma by inducing aromatase expression under some conditions. These results provide new insights on the possible roles of environmental toxins in breast cancer development.

Keywords

Breast cancer Aryl hydrocarbon receptor Aromatase Estrogen receptor pathway 

Abbreviations

AhR

Aryl hydrocarbon receptor

Beta-NF

Beta-naphthoflavone

BRCA1

Breast cancer susceptibility gene 1

CYP

Cytochrome P450

DAB

3,3′-Diaminobenzidine

DMSO

Dimethyl sulfoxide

E1

Estrone

E2

Estradiol

ER

Estrogen receptor

FBS

Fetal bovine serum

IDC

Invasive ductal carcinoma

IL-6

Interleukin-6

OD

Optical density

pS2

Estrogen-inducible protein pS2

RPL13A

Ribosomal protein L13a

TCDD

2,3,7,8-Tetrachlorodibenzo-p-dioxin

TNF

Tumor necrosis factor

Notes

Acknowledgements

We gratefully acknowledge Mr. Katsuhiko Ono and Erina Iwabuchi (Tohoku University School of Medicine) for providing excellent technical support.

Compliance with ethical statements

Conflict of interest

The authors declare that they do not have any conflict of interest.

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Ryoko Saito
    • 1
    Email author
  • Yasuhiro Miki
    • 1
  • Shuko Hata
    • 1
  • Takanori Ishida
    • 2
  • Takashi Suzuki
    • 3
  • Noriaki Ohuchi
    • 2
  • Hironobu Sasano
    • 1
  1. 1.Department of PathologyTohoku University School of MedicineSendaiJapan
  2. 2.Department of SurgeryTohoku University HospitalSendaiJapan
  3. 3.Department of Pathology and HistotechnologyTohoku University School of MedicineSendaiJapan

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