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Research ArticleExperimental Studies

Chemokine (C-C motif) Ligand 2 Is Regulated Through the EGFR/Src Pathway in HER2-positive Breast Cancer Cells

DAEUN YOU, HYUNGJOO KIM, YISUN JEONG, SUN YOUNG YOON, EUNJI LO, JEONG EON LEE and SANGMIN KIM
Anticancer Research March 2023, 43 (3) 1079-1089; DOI: https://doi.org/10.21873/anticanres.16253
DAEUN YOU
1Department of Breast Cancer Center, Samsung Medical Center, Seoul, Republic of Korea;
2Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea;
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HYUNGJOO KIM
1Department of Breast Cancer Center, Samsung Medical Center, Seoul, Republic of Korea;
2Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea;
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YISUN JEONG
1Department of Breast Cancer Center, Samsung Medical Center, Seoul, Republic of Korea;
3Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea
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SUN YOUNG YOON
1Department of Breast Cancer Center, Samsung Medical Center, Seoul, Republic of Korea;
3Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea
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EUNJI LO
1Department of Breast Cancer Center, Samsung Medical Center, Seoul, Republic of Korea;
3Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea
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JEONG EON LEE
1Department of Breast Cancer Center, Samsung Medical Center, Seoul, Republic of Korea;
2Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea;
3Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea
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  • For correspondence: paojlus@hanmail.ne
SANGMIN KIM
1Department of Breast Cancer Center, Samsung Medical Center, Seoul, Republic of Korea;
2Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea;
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  • For correspondence: sangmin3005.kim@samsung.com
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Abstract

Background/Aim: Chemokine (C-C motif) ligand 2 (CCL2) influences growth and metastasis and is associated with poor prognosis in various cancers. However, the regulatory mechanism of CCL2 induction by human epidermal growth factor receptor 2 (HER2) is not fully understood in breast cancer. Thus, we investigated how CCL2 expression is regulated in HER2-positive (HER2+) breast cancer. Materials and Methods: A human cytokine array was performed to investigate the differential expression of cytokines by HER2 overexpression. Quantitative reverse transcription PCR, enzyme-linked immunosorbent assay and western blot were performed to detect the levels of mRNA and protein expression. Cell cycle and proliferation were analyzed by flow cytometry. Cell invasion was analyzed by Boyden chamber assay. Results: Our results showed that HER2 overexpression augmented CCL2 expression. Epidermal growth factor receptor (EGFR) and Src activities were increased in the HER2-overexpressed breast cancer cells. Interestingly, HER2-induced CCL2 expression could not be down-regulated by trastuzumab, while neratinib or saracatinib led to a decrease in the expression of CCL2 in HER2+ breast cancer cells. Conclusion: CCL2 expression is regulated through the EGFR/Src-dependent signaling in HER2+ breast cancer.

Key Words:
  • Chemokine (C-C motif) ligand 2
  • C-C chemokine receptor type 2
  • epidermal growth factor receptor
  • human epidermal growth factor receptor 2
  • Src
  • Received January 3, 2023.
  • Revision received January 20, 2023.
  • Accepted January 24, 2023.
  • Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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Chemokine (C-C motif) Ligand 2 Is Regulated Through the EGFR/Src Pathway in HER2-positive Breast Cancer Cells
DAEUN YOU, HYUNGJOO KIM, YISUN JEONG, SUN YOUNG YOON, EUNJI LO, JEONG EON LEE, SANGMIN KIM
Anticancer Research Mar 2023, 43 (3) 1079-1089; DOI: 10.21873/anticanres.16253

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Chemokine (C-C motif) Ligand 2 Is Regulated Through the EGFR/Src Pathway in HER2-positive Breast Cancer Cells
DAEUN YOU, HYUNGJOO KIM, YISUN JEONG, SUN YOUNG YOON, EUNJI LO, JEONG EON LEE, SANGMIN KIM
Anticancer Research Mar 2023, 43 (3) 1079-1089; DOI: 10.21873/anticanres.16253
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Keywords

  • Chemokine (C-C motif) ligand 2
  • C-C chemokine receptor type 2
  • epidermal growth factor receptor
  • human epidermal growth factor receptor 2
  • Src
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