Upregulation of GPR34 expression affects the progression and prognosis of human gastric adenocarcinoma by PI3K/PDK1/AKT pathway.

Abstract

PURPOSE:

G-protein coupled receptor 34 (GPR34), which belongs to the G-protein coupled receptors superfamily, is reportedly expressed highly in the spread of several solid tumors. However, its expression in gastric primary tumor and potential role in gastric cancer development and progression have not been determined.

METHODS:

Immunohistochemistry, real-time RT-PCR and western blot methods were used to determine GPR34 expression in human gastric cancer tissues/cell lines and matched adjacent tissues/ normal mucosal cell line. A statistical analysis was performed to establish the potential correlation between GPR34 expression and the patients' clinicopathological characteristics, tumor progression, and prognosis. Stably transfected NCI-N87 cell lines with either GPR34 over-expression or knock-down were constructed to determine the effect of GPR34 on gastric cancer cell invasion and migration, and to explain the preliminary molecular mechanism of GPR34 in gastric cancer metastasis.

RESULTS:

GPR34 is up-regulated in primary gastric cancer tissues/cell lines compared with matched adjacent tissues/normal mucosal cell line, and when the relationship between GPR34 expression and the the clinicopathological characteristics was analyzed, it was shown that GPR34 expression is significantly correlated with tumor differentiation, infiltration depth, and lymph node status and had a significant influence on prognosis. Furthermore, GPR34-overexpression increased while GPR34-knockdown inhibited NCI-N87 cell invasion in vitro by PI3K/PDK1/AKT pathway.

CONCLUSIONS:

Taken together, up-regulation of GPR34 expression in human gastric carcinoma may play a critical role in tumor progression and in determining patient prognosis. GPR34 may be a useful diagnostic or prognostic molecular biomarker, and a potential target for therapeutic intervention.

• Authors: Weidong Yu, Shuyun Ma, Lihong Wang, Bo Zuo, Mei Li, Zhengguo Qiao, Xiuying Pan, Yulan Liu, Jingtong Wang
• Journal: Histology and histopathology (Histol Histopathol) Vol. 28 Issue 12 Pg. 1629-38 (12 2013) ISSN: 1699-5848 [Electronic] Spain
• PMID: 23836308 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• Elafin
• G-protein-coupled receptor 34
• PDK1 protein, human
• PI3 protein, human
• Pyruvate Dehydrogenase Acetyl-Transferring Kinase
• Receptors, Lysophospholipid
• Protein Serine-Threonine Kinases
• Proto-Oncogene Proteins c-akt

Topics

• Adenocarcinoma (metabolism, pathology)
• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor (analysis)
• Blotting, Western
• Disease Progression
• Elafin (metabolism)
• Female
• Humans
• Immunohistochemistry
• Male
• Middle Aged
• Prognosis
• Protein Serine-Threonine Kinases (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Pyruvate Dehydrogenase Acetyl-Transferring Kinase
• Real-Time Polymerase Chain Reaction
• Receptors, Lysophospholipid (biosynthesis)
• Retrospective Studies
• Reverse Transcriptase Polymerase Chain Reaction
• Signal Transduction (physiology)
• Stomach Neoplasms (metabolism, pathology)
• Up-Regulation
• Young Adult