SH3GL2 gene participates in MEK-ERK signal pathway partly by regulating EGFR in the laryngeal carcinoma cell line Hep2.
BACKGROUND
The human Src homology 3 (SH3) domain GRB2-like 2 (SH3GL2) gene, a novel tumor suppressor gene in laryngeal squamous cell carcinoma (LSCC), induces apoptosis of tumor cells by regulating intra-cellular signal transduction networks. The objective of this study was to investigate the molecular mechanism of SH3GL2 in laryngeal carcinogenesis.


METHODS
RNA interference inhibited the expression of level of SH3GL, and RT-PCR and Western blotting were applied to evaluate the expression level of SH3GL2 after RNA interference. After RNA interference, flow cytometry and 3-(4,5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT) assay were used to detect the biological effects, and Western blotting was used to determine the expression of EGFR and phosphorylated ERK1/2. The Hep2 cells transfected with siRNA-SH3GL2 were treated by U0126 (selective MEK1/2 Inhibitor), and the phosphorylated ERK1/2 proteins were detected by Western blotting; cell proliferation and apoptosis were detected subsequently.


RESULTS
Our results show that the expression level of epidermal growth factor receptor (EGFR) and phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2) were up-regulated after down-regulation of SH3GL2. Additionally, SH3GL2 promoted apoptosis while decreasing cell proliferation. However, if ERK1/2 was inhibited by U0126, the apoptosis rate increased and proliferation decreased inversely.


CONCLUSIONS
SH3GL2 participates in the regulation of apoptosis through the MEK-ERK signal pathway by adjusting EGFR in the laryngeal carcinoma cell line Hep2.
Department of Neurobiology, China Medical University, Shenyang, PR China.
Chao
C
Shang
Yan
Y
Guo
Shuang
S
Fu
Weineng
W
Fu
Kailai
K
Sun
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000502:physiology*; D017209:Apoptosis; D045744:Cell Line, Tumor; D017931:DNA Primers / Q000235:genetics; D066246:ErbB Receptors / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007822:Laryngeal Neoplasms / Q000175:diagnosis*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D008954:Models, Biological; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
D048868:Adaptor Proteins, Signal Transducing; D017931:DNA Primers; D034741:RNA, Small Interfering; C107640:SH3GL2 protein, human; D066246:ErbB Receptors; D048052:Mitogen-Activated Protein Kinase 3; D020929:Mitogen-Activated Protein Kinase Kinases