The roles of BTG3 expression in gastric cancer: a potential marker for carcinogenesis and a target molecule for gene therapy

Autor: Shuang Zhao, Wen-feng Gou, Yunpeng Liu, Hong-zhi Sun, Hua-chuan Zheng, Rong-jian Su, Xue-feng Yang, Yasuo Takano, Jun-sheng Luo, Dao-fu Shen
Rok vydání: 2015
Předmět:
Male
Time Factors
Angiogenesis
Cellular differentiation
Apoptosis
Cell Cycle Proteins
medicine.disease_cause
Metastasis
Cell Movement
BTG3
Medicine
Aged
80 and over
Mice
Inbred BALB C
Cell Differentiation
Middle Aged
gene therapy
G2 Phase Cell Cycle Checkpoints
Gene Expression Regulation
Neoplastic
Phenotype
Oncology
Female
carcinogenesis
medicine.drug
Signal Transduction
Research Paper
Adult
pathobiological behaviors
Mice
Nude
Antineoplastic Agents
Adenocarcinoma
Transfection
Young Adult
Stomach Neoplasms
Cell Line
Tumor
Autophagy
Biomarkers
Tumor
Animals
Humans
Neoplasm Invasiveness
RNA
Messenger
Aged
Cell Proliferation
Cisplatin
Dose-Response Relationship
Drug
business.industry
gastric cancer
Cancer
Proteins
Genetic Therapy
DNA Methylation
medicine.disease
Immunology
Cancer cell
Cancer research
business
Carcinogenesis
Apoptosis Regulatory Proteins
Zdroj: Oncotarget
ISSN: 1949-2553
Popis: BTG (B-cell translocation gene) can inhibit cell proliferation, metastasis and angiogenesis, cell cycle progression, and induce differentiation in various cells. Here, we found that BTG3 overexpression inhibited proliferation, induced S/G2 arrest, differentiation, autophagy, apoptosis, suppressed migration and invasion in MKN28 and MGC803 cells (p < 0.05). BTG3 transfectants showed a higher mRNA expression of p27, Bax, 14-3-3, Caspase-3, Caspase-9, Beclin 1, NF-κB, IL-1, -2, -4, -10 and -17, but a lower mRNA expression of p21, MMP-9 and VEGF than the control and mock (p < 0.05). At protein level, BTG3 overexpression increased the expression of CDK4, AIF, LC-3B, Beclin 1 and p38 (p < 0.05), but decreased the expression of p21 and β-catenin in both transfectants (p < 0.05). After treated with cisplatin, MG132, paclitaxel and SAHA, both BTG3 transfectants showed lower viability and higher apoptosis than the control in both time- and dose-dependent manners (p < 0.05). BTG3 expression was restored after 5-aza-2'-deoxycytidine or MG132 treatment in gastric cancer cells. BTG3 expression was decreased in gastric cancer in comparison to the adjacent mucosa (p < 0.05), and positively correlated with venous invasion and dedifferentiation of cancer (p < 0.05). It was suggested that BTG3 expression might contribute to gastric carcinogenesis. BTG3 overexpression might reverse the aggressive phenotypes and be employed as a potential target for gene therapy of gastric cancer.
Databáze: OpenAIRE
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