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

Ehsan Mokhtari1, Hesamodin Mokhtari2, Elham Moslemi1

  • 1Department of Biology, Faculty of Biological Sciences, Islamic Azad University, East Tehran Branch, Tehran, Iran.

Avicenna Journal of Medical Biotechnology
|December 18, 2018
PubMed
Abstract

Insights

Human Epidermal growth factor Receptor-3 (HER-3) is overexpressed in gastric cancer, correlating with invasion depth. Knocking down HER-3 in MKN45 cells reduced viability and increased G2/M phase accumulation, highlighting its role in gastric adenocarcinoma.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Human Epidermal growth factor Receptor-3 (HER-3), a member of the ErbB family, lacks kinase activity but is crucial for downstream signaling via heterodimerization, particularly with HER-2.
  • HER-3 is frequently co-expressed and overexpressed in various cancers, often coinciding with activated oncogenic pathways like Jak/Stat, MAPK, and PI3K/Akt.
  • This study focuses on HER-3's role in gastric adenocarcinoma, a prevalent cancer type.

Purpose of the Study:

  • To investigate the expression level of HER-3 in Iranian gastric adenocarcinoma patients.
  • To determine the effects of HER-3 knockdown on the cell cycle and cell viability of the MKN45 gastric adenocarcinoma cell line.

Main Methods:

  • Analysis of 38 gastric adenocarcinoma specimens and adjacent non-tumor tissues using real-time PCR to quantify HER-3 expression.
  • Transfection of MKN45 cells with siRNA targeting HER-3 to achieve gene knockdown.
  • Evaluation of cell viability using MTT assay and cell cycle analysis post-HER-3 knockdown.

Main Results:

  • HER-3 was significantly overexpressed in gastric tumors compared to non-tumor tissues.
  • HER-3 expression levels positively correlated with tumor depth of invasion.
  • HER-3 knockdown in MKN45 cells led to increased G2/M phase cell cycle arrest and decreased cell viability.

Conclusions:

  • The findings underscore the significant role of HER-3 in the tumorigenesis of gastric adenocarcinoma.
  • HER-3 receptor status is important for the diagnosis and prognosis of gastric adenocarcinoma.
  • Targeting HER-3 may represent a potential therapeutic strategy for gastric cancer.
Keywords:
Epidermal growth factor receptorGastric adenocarcinomaHER-3Iran

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