Title |
HER2 induces cell proliferation and invasion of non-small-cell lung cancer by upregulating COX-2 expression via MEK/ERK signaling pathway
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Published in |
OncoTargets and therapy, May 2016
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DOI | 10.2147/ott.s96197 |
Pubmed ID | |
Authors |
Feng Chi, Rong Wu, Xueying Jin, Min Jiang, Xike Zhu |
Abstract |
HER2 positivity has been well studied in various cancers, but its importance in non-small-cell lung cancer (NSCLC) is still being explored. In this study, quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to detect HER2 and COX-2 expression in NSCLC tissues. Then, pcDNA3.1-HER2 was used to overexpress HER2, while HER2 siRNA and COX-2 siRNA were used to silence HER2 and COX-2 expression. MTT assay and invasion assay were used to detect the effects of HER2 on cell proliferation and invasion. Our study revealed that HER2 and COX-2 expression were upregulated in NSCLC tissues and HER2 exhibited a significant positive correlation with the levels of COX-2 expression. Overexpression of HER2 evidently elevated COX-2 expression, while silencing of HER2 evidently decreased COX-2 expression. Furthermore, overexpressed HER2 induced the ERK phosphorylation, and this was abolished by the treatment with U0126, a pharmacological inhibitor of MEK, an upstream kinase of ERK. HER2-induced expression and promoter activity of COX-2 were also suppressed by U0126, suggesting that the MEK/ERK signaling pathway regulates COX-2 expression. In addition, HER2 induced activation of AKT signaling pathway, which was reversed by pretreatment with U0126 and COX-2 siRNA. MTT and invasion assays revealed that HER2 induced cell proliferation and invasion that were reversed by pretreatment with U0126 and COX-2 siRNA. In this study, our results demonstrated for the first time that HER2 elevated COX-2 expression through the activation of MEK/ERK pathway, which subsequently induced cell proliferation and invasion via AKT pathway in NSCLC tissues. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 17 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Bachelor | 4 | 24% |
Student > Doctoral Student | 3 | 18% |
Student > Master | 3 | 18% |
Student > Ph. D. Student | 1 | 6% |
Unspecified | 1 | 6% |
Other | 2 | 12% |
Unknown | 3 | 18% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 5 | 29% |
Agricultural and Biological Sciences | 3 | 18% |
Pharmacology, Toxicology and Pharmaceutical Science | 2 | 12% |
Unspecified | 1 | 6% |
Veterinary Science and Veterinary Medicine | 1 | 6% |
Other | 0 | 0% |
Unknown | 5 | 29% |