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Article Open Access

Primary bile acid activates Egr‑1 expression through the MAPK signaling pathway in gastric cancer

  • Authors:
    • Su-Mi Lee
    • Moon Sik Park
    • Seon-Young Park
    • Yoo-Duk Choi
    • Jin Ook Chung
    • Dong Hyun Kim
    • Young Do Jung
    • Hyun Soo Kim
  • View Affiliations / Copyright

    Affiliations: Division of Gastroenterology, Department of Internal Medicine, Chonnam National University Medical School, Gwangju 61469, Republic of Korea, Department of Pathology, Chonnam National University Medical School, Gwangju 61469, Republic of Korea, Division of Endocrinology, Department of Internal Medicine, Chonnam National University Medical School, Gwangju 61469, Republic of Korea, Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju 61469, Republic of Korea
    Copyright: © Lee et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 129
    |
    Published online on: February 15, 2022
       https://doi.org/10.3892/mmr.2022.12646
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Abstract

Bile acids have been linked to pathomechanism and prognosis in various types of cancers. The present study aimed to investigate the effect of bile acids on the molecular change in gastric epithelial cancer cells and to evaluate gastric bile acid concentration in patients with early gastric cancer (EGC). Human gastric cancer cells (AGS and NCI‑N87 cell lines) were treated with several bile acid types to determine their effect on molecular changes in the cells. Gastric levels of individual bile acids were measured (primary unconjugated or conjugated bile acids and secondary bile acids) in 39 participants (20 controls and 19 patients with EGC). Exposing gastric epithelial cancer cells to primary bile acids in vitro upregulated the expression of early growth response factor 1 (Egr‑1) and the oncogenes including c‑Jun, c‑Myc and Snail, whereas a p42/44 MAPK inhibitor exposure reduced their expression. There was a significant difference in age and presence of atrophic gastritis with intestinal metaplasia in background mucosa between controls and patients with EGC. There were significant differences in the levels of unconjugated or conjugated primary bile acids between controls and EGC patients except lithocholic acid. After adjustment of age and presence of atrophic gastritis with intestinal metaplasia, the levels of cholic acid [adjusted odds ratio (aOR) 4.3; 95% confidence interval (CI): 1.2‑16.2; P=0.029] and glycochenodeoxycholic acid [aOR 9.9; 95% CI: 1.3‑75.3; P=0.027] were significantly higher in patients with EGC compared with controls. In conclusion, bile acids upregulate Egr‑1 in gastric cancer cells via the MAPK signaling pathway, and higher gastric levels of primary bile acids are associated with EGC. Therefore, exposure of gastric cells to primary bile acids may play a role in gastric carcinogenesis.
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Copy and paste a formatted citation
Spandidos Publications style
Lee S, Park MS, Park S, Choi Y, Chung JO, Kim DH, Jung YD and Kim HS: Primary bile acid activates Egr‑1 expression through the MAPK signaling pathway in gastric cancer. Mol Med Rep 25: 129, 2022.
APA
Lee, S., Park, M.S., Park, S., Choi, Y., Chung, J.O., Kim, D.H. ... Kim, H.S. (2022). Primary bile acid activates Egr‑1 expression through the MAPK signaling pathway in gastric cancer. Molecular Medicine Reports, 25, 129. https://doi.org/10.3892/mmr.2022.12646
MLA
Lee, S., Park, M. S., Park, S., Choi, Y., Chung, J. O., Kim, D. H., Jung, Y. D., Kim, H. S."Primary bile acid activates Egr‑1 expression through the MAPK signaling pathway in gastric cancer". Molecular Medicine Reports 25.4 (2022): 129.
Chicago
Lee, S., Park, M. S., Park, S., Choi, Y., Chung, J. O., Kim, D. H., Jung, Y. D., Kim, H. S."Primary bile acid activates Egr‑1 expression through the MAPK signaling pathway in gastric cancer". Molecular Medicine Reports 25, no. 4 (2022): 129. https://doi.org/10.3892/mmr.2022.12646
Copy and paste a formatted citation
x
Spandidos Publications style
Lee S, Park MS, Park S, Choi Y, Chung JO, Kim DH, Jung YD and Kim HS: Primary bile acid activates Egr‑1 expression through the MAPK signaling pathway in gastric cancer. Mol Med Rep 25: 129, 2022.
APA
Lee, S., Park, M.S., Park, S., Choi, Y., Chung, J.O., Kim, D.H. ... Kim, H.S. (2022). Primary bile acid activates Egr‑1 expression through the MAPK signaling pathway in gastric cancer. Molecular Medicine Reports, 25, 129. https://doi.org/10.3892/mmr.2022.12646
MLA
Lee, S., Park, M. S., Park, S., Choi, Y., Chung, J. O., Kim, D. H., Jung, Y. D., Kim, H. S."Primary bile acid activates Egr‑1 expression through the MAPK signaling pathway in gastric cancer". Molecular Medicine Reports 25.4 (2022): 129.
Chicago
Lee, S., Park, M. S., Park, S., Choi, Y., Chung, J. O., Kim, D. H., Jung, Y. D., Kim, H. S."Primary bile acid activates Egr‑1 expression through the MAPK signaling pathway in gastric cancer". Molecular Medicine Reports 25, no. 4 (2022): 129. https://doi.org/10.3892/mmr.2022.12646
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