Effect of GPR87 on cell proliferation via KRAS signaling pathway in p53-mutant lung cancer cells.

Abstract

e14713 Background: GPR87 is a member of the cell surface molecular G protein-coupled receptors (GPCRs) family and suggested to contribute to the viability of human tumor cells including lung cancer cell. The mechanism of GPR87 in promote cell proliferation is still not yet well understand. p53 was reported to take an important role in keeping cell viability of GPR87-expressing cells. However, most of lung cancer cells possess p53 mutation. In the present study, several reported signal pathway were investigated in lung cancer cells. Methods: Two p53 mutant GPR87-overexpressing lung cancer cell H358 and PC9 lung cancer cell was investigated. An adenoviral vector that encoded a short hairpin siRNA targeting the GPR87 gene (Ad-shGPR87) was constructed. Real-time RT-PCR was performed to evaluate gene expressions and westen blotting analysis for protein expression. MTT assay was used to evaluate the cell viability. Results: Ad-shGPR87 effectively inhibited the GPR87 expression and significantly reduced the percentage of viable cells in GPR87-overexpression H358 and PC9 cell. Regading the signal pathway, there was no p53 expression in H358 cell and no changes in PC9 cell. However, both cells showed a significant decrease in KRAS and c-Myc gene expression 5 days after Ad-shGPR87 transfection. On the other hand, after Ad-shGPR87 transfection, Akt and Cyclin-D1gene expression decrease slightly in H358, but not in the PC9 cell. Conclusions: Theses result show that GPR87 may promoting cell proliferation through several signaling pathways and that the active in p53 mutant cell may linked to KRAS pathway in lung cancer cell.