BAG3 contributes to HGF-mediated cell proliferation, migration, and invasion via the Egr1 pathway in gastric cancer.

Abstract

INTRODUCTION::

Bcl2-associated athanogene 3 (BAG3) is elevated in several types of cancers. However, the role of BAG3 in progression of gastric cancer is unknown. Therefore, the present study aims to find out the role of BAG3 in hepatocyte growth factor (HGF)-mediated tumor progression and the molecular mechanisms by which HGF regulates BAG3 expression.

METHODS::

BAG3 mRNA and protein were measured using reverse transcription polymerase chain reaction and Western blot in the 2 human gastric cancer cell lines, NUGC3 and MKN28, treated with or without HGF. The effects of BAG3 knockdown on cell proliferation, cell invasion, and apoptosis were analyzed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, the in vitro 2-chamber invasion assay, and flow cytometry in BAG3 short hairpin RNA (shRNA)-transfected cells and control cells. The signaling pathways involved in BAG3 that are regulated by HGF were analyzed. The chromatin immunoprecipitation assay was used to determine binding of Egr1 to the BAG3 promoter.

RESULTS::

BAG3 mRNA and protein levels were increased following treatment with HGF. HGF-mediated BAG3 upregulation increased cell proliferation and cell invasion; however, it decreased apoptosis. HGF-mediated BAG3 upregulation is regulated by an ERK and Egr1-dependent pathway. BAG3 may have an important role in HGF-mediated cell proliferation and metastasis in gastric cancer through an ERK and Egr1-dependent pathway.

CONCLUSION::

This pathway may provide novel therapeutic targets and provide information for further identification of other targets of therapeutic significance in gastric cancer.

• Authors: Jae Chang Lee, Sung Ae Koh, Kyung Hee Lee, Jae-Ryong Kim
• Journal: Tumori (Tumori) Vol. 105 Issue 1 Pg. 63-75 (Feb 2019) ISSN: 2038-2529 [Electronic] United States
• PMID: 30514177 (Publication Type: Journal Article)

Chemical References

• Adaptor Proteins, Signal Transducing
• Apoptosis Regulatory Proteins
• BAG3 protein, human
• EGR1 protein, human
• Early Growth Response Protein 1
• HGF protein, human
• RNA, Messenger
• RNA, Small Interfering
• Hepatocyte Growth Factor

Topics

• Adaptor Proteins, Signal Transducing (metabolism)
• Apoptosis (physiology)
• Apoptosis Regulatory Proteins (metabolism)
• Cell Line, Tumor
• Cell Movement (physiology)
• Cell Proliferation (physiology)
• Early Growth Response Protein 1 (metabolism)
• Gene Expression Regulation, Neoplastic (genetics)
• Hepatocyte Growth Factor (metabolism)
• Humans
• Neoplasm Invasiveness (pathology)
• Promoter Regions, Genetic (genetics)
• RNA, Messenger (genetics)
• RNA, Small Interfering (genetics)
• Signal Transduction (physiology)
• Stomach Neoplasms (genetics, metabolism, pathology)
• Up-Regulation (genetics)