» Articles » PMID: 30555655

HER-3 Knocking Down Induces G2/M Arrest in Gastric Cancer Cells

Overview
Date 2018 Dec 18
PMID 30555655
Citations 1
Authors
Affiliations
Soon will be listed here.
Abstract

Background: The Human Epidermal growth factor Receptor-3 (HER-3) is a member of ErbB receptor family and has deficient kinase activity. HER-3 should heterodimerize with other members of ErbB receptor family, especially with HER-2, to transduce downstream signaling pathways. HER-3 co-expresses with other ErbB receptors in different cancers and overexpresses while the oncogenic signaling pathways such as Jak/Stat, MAPK, and PI3K/Akt are activated and promoted. Here, the expression level of HER-3 was evaluated in Iranian gastric adenocarcinoma's patients and the effects of HER-3 knocking down was investigated on cell cycle and cell viability of human gastric adenocarcinoma cell line of MKN45.

Methods: In this study, 38 paraffin-embedded surgical adenocarcinoma specimens and their marginal non-tumor tissue samples were collected. Total RNAs were extracted and cDNAs were synthesized. Finally, the expression level of HER-3 was evaluated by real time PCR approach. Moreover, the human adenocarcinoma cell line of MKN45 was transfected with siRNA against HER-3 and the effects of its down-regulation were evaluated using MTT assay and cell-cycle analysis.

Results: The data obtained from this study revealed HER-3 is significantly overexpressed in gastric tumors rather than non-tumor marginal tissues. Also, it was found that the expression level of HER-3 is elevated with tumor depth of invasion. Moreover, HER-3 knocking down promotes cell accumulation in G2/M phase of cell cycle and decreases cell viability in MKN45 cells which suggests a potential role for HER-3 in gastric adenocarcinoma tumorigenesis.

Conclusion: Taken together, these results emphasize the importance of HER-3 receptor in diagnosis and prognosis of gastric adenocarcinoma.

Citing Articles

Hippo signaling and histone methylation control cardiomyocyte cell cycle re-entry through distinct transcriptional pathways.

Zhang Z, Freeman M, Zhang Y, El-Nachef D, Davenport G, Williams A PLoS One. 2023; 18(2):e0281610.

PMID: 36780463 PMC: 9925018. DOI: 10.1371/journal.pone.0281610.

References
1.
Klapper L, Kirschbaum M, Sela M, Yarden Y . Biochemical and clinical implications of the ErbB/HER signaling network of growth factor receptors. Adv Cancer Res. 1999; 77:25-79. View

2.
Xia W, Lau Y, Zhang H, Xiao F, Johnston D, Liu A . Combination of EGFR, HER-2/neu, and HER-3 is a stronger predictor for the outcome of oral squamous cell carcinoma than any individual family members. Clin Cancer Res. 2000; 5(12):4164-74. View

3.
Hubbard S, Till J . Protein tyrosine kinase structure and function. Annu Rev Biochem. 2000; 69:373-98. DOI: 10.1146/annurev.biochem.69.1.373. View

4.
Mendelsohn J, Baselga J . The EGF receptor family as targets for cancer therapy. Oncogene. 2001; 19(56):6550-65. DOI: 10.1038/sj.onc.1204082. View

5.
Citri A, Skaria K, Yarden Y . The deaf and the dumb: the biology of ErbB-2 and ErbB-3. Exp Cell Res. 2003; 284(1):54-65. DOI: 10.1016/s0014-4827(02)00101-5. View