G Protein-Coupled Receptor 87 (GPR87) Promotes Cell Proliferation in Human Bladder Cancer Cells

Autor: Takeshi Hashimoto, Mikio Sugimoto, Dage Liu, Xia-Xia Zhang, Homare Okazoe, Nobufumi Ueda, Yoshiyuki Kakehi, Yushi Hayashida
Jazyk: angličtina
Rok vydání: 2015
Předmět:
p53
Cell
Apoptosis
Mice
SCID
Metastasis
Small hairpin RNA
lcsh:Chemistry
Mice
shRNA
Adenovirus
RNA
Small Interfering
Receptors
Lysophosphatidic Acid
lcsh:QH301-705.5
Spectroscopy
GPR87
General Medicine
gene therapy
Computer Science Applications
medicine.anatomical_structure
RNA Interference
Signal transduction
Signal Transduction
Cyclin-Dependent Kinase Inhibitor p21
Cell Survival
Transplantation
Heterologous
Biology
Catalysis
Article
Inorganic Chemistry
Cell Line
Tumor
medicine
Animals
Humans
Physical and Theoretical Chemistry
xenograft
Molecular Biology
Cell Proliferation
Bladder cancer
Cell growth
Organic Chemistry
medicine.disease
Molecular biology
lcsh:Biology (General)
lcsh:QD1-999
Urinary Bladder Neoplasms
Cell culture
Cancer cell
Cancer research
Tumor Suppressor Protein p53
Neoplasm Transplantation
Zdroj: International Journal of Molecular Sciences
International Journal of Molecular Sciences, Vol 16, Iss 10, Pp 24319-24331 (2015)
Volume 16
Issue 10
Pages 24319-24331
ISSN: 1422-0067
Popis: G protein-coupled receptor 87 (GPR87) is a newly deorphanized member of the cell surface molecule G protein-coupled receptor family. GPR signaling was shown to play a role in promotion of cell growth and survival, metastasis, and drug resistance. The overexpression of GPR87 has also been reported in many malignant tumors including bladder cancer. The aim of the present study is to examine the effect of silencing GPR87 expression with a replication-deficient recombinant adenoviral vector expressing short hairpin RNA targeting GPR87 (Ad-shGPR87) and to explore the underlying molecular mechanisms in bladder cancer cells. Six GPR87-expressing human bladder cancer cells, HT1197, HT1376, J82, RT112, TCCSUP and UMUC3, were used. Infection with Ad-shGPR87 effectively downregulated the GPR87 expression, and significantly reduced the percentage of viable cells in 4 of 6 cell lines as detected by an MTT assay. Significant inhibition on cell proliferation with Ad-shGPR87 was observed in the wild-type p53 bladder cancer cell lines (HT1197, RT112, TCCSUP and UMUC3), but not in the mutant p53 cells (HT1376 and J82). As represented by a wild-type p53 RT112 cell, Ad-shGPR87 infection significantly enhanced p53 and p21 expression and caused caspase-dependent apoptosis. Furthermore, the treatment with Ad-shGPR87 exerted a significant antitumor effect against the GPR87-expressing RT112 xenografts. GPR87 appeared to be a promising target for gene therapy, and Ad-shGPR87 had strong antitumor effects, specifically anti-proliferative and pro-apoptotic effects, against GPR87-expressing human bladder cancer cells.
Databáze: OpenAIRE
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