Heregulin-induced cell migration is promoted by aryl hydrocarbon receptor in HER2-overexpressing breast cancer cells

Journal Article · Tue May 15 04:00:00 EDT 2018 · Experimental Cell Research

DOI:https://doi.org/10.1016/J.YEXCR.2018.02.033· OSTI ID:23082402

Yamashita, Naoya; Saito, Nao; Zhao, Shuai ^[1]; Terai, Kensuke; Hiruta, Nobuyuki ^[2]; Park, Youngjin ^[3]; Bujo, Hideaki ^[2]; Nemoto, Kiyomitsu ^[1]; Kanno, Yuichiro ^[4]

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1. Department of Molecular Toxicology, Faculty of Pharmaceutical Sciences, Toho University, Miyama 2-2-1, Funabashi, Chiba 274-8510 (Japan)
2. Department of Clinical-Laboratory and Experimental-Research Medicine, Toho University Sakura Medical Center, Shimoshizu 564-1, Sakura, Chiba 285-8741 (Japan)
3. Department of Surgery, Toho University Sakura Medical Center, Shimoshizu 564-1, Sakura, Chiba 285-8741 (Japan)
4. Department of Breast and Endocrine Surgery, Tohoku Medical and Pharmaceutical University, Fukumuro 1-15-1, Miyagino-ku, Sendai, Miyagi prefecture, 983-8536 (Japan)

Highlights: • Heregulin signaling up-regulates AhR expression at the transcriptional level in HER2-overexpressing breast cancer cells. • Heregulin signaling induces nuclear translocation of AhR. • Knockout of the AhR decreases cell migration by heregulin signaling in HER2-overexpressing breast cancer cells. HER2 overexpression accounts for approximately 15–20% of all breast cancers. We have shown that HER2 overexpression leads to elevated expression of the aryl hydrocarbon receptor (AhR) in breast cancer cells. In this study, firstly, we showed that AhR expression was up-regulated by treatment with the HER3 ligand heregulin (HRG) in HER2-overexpressing breast cancer cell lines. Induction of AhR was mediated by transcriptional activation of the region of AhR promoter corresponding to − 190 to − 100 bp. In addition, HRG treatment elicited nuclear translocation of AhR. To investigate the role of AhR in HRG-HER2/HER3 signaling in HER2-overexpressing cells, we established AhR knockout (KO) HER2-overexpressing cells to perform wound-healing assays. HRG-induced cell migration was markedly attenuated by AhR KO. HRG-induced cell migration was associated with increased expression of the inflammatory cytokines interleukin (IL)-6 and IL-8 in wild type cells, but not in AhR KO cells. These results elucidate that AhR is an important factor for the malignancy in HER2 overexpressing breast cancers.

• OSTI ID: 23082402
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 1 Vol. 366; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
HEALING
INFLAMMATION
LYMPHOKINES
MAMMARY GLANDS
NEOPLASMS
WOUNDS