MEK5 overexpression is associated with the occurrence and development of colorectal cancer
Open Access
- 9 May 2016
- journal article
- research article
- Published by Springer Nature in BMC Cancer
- Vol. 16 (1) , 1-12
Abstract
Mitogen/extracellular signal-regulated kinase kinase-5 (MEK5) has been confirmed to play a pivotal role in tumor carcinogenesis and progression. However, few studies have investigated the role of MEK5 in colorectal cancer (CRC). MEK5 expression was determined by immunohistochemistry (IHC) in tissue microarrays (TMAs) containing 2 groups of tissues, and western blotting was used to confirm MEK5 expression in 8 cases of primary CRC tissues and paired normal mucosa. RNA interference was used to verify the biological function of MEK5 gene in the development of CRC. IHC revealed the expression of MEK5 was higher in tumor tissues (38.1 %), compared with adjacent normal tissue (8.3 %). Western blot showed that, MEK5 expression was upregulated in CRC tumor tissues compared with normal tissue. Analysis of clinical pathology parameters indicated MEK5 overexpression was significantly correlated with the depth of invasion, lymph node metastasis, distant metastasis and histological grade. Survival analysis revealed that MEK5 overexpression negatively correlated with cancer-free survival (hazard ratio 1.64, P = 0.017). RNA interference-mediated knockdown of MEK5 in SW480 colon cancer cells decreased their proliferation, division, migration and invasiveness in vitro and slowed down tumors growth in mice engrafted with the cells. MEK5 plays an important role in CRC progression and may be a potential molecular target for the treatment of CRC.Keywords
Funding Information
- Guangdong Province Natural Science Foundation of China (S2013040016396)
This publication has 28 references indexed in Scilit:
- Cancer statistics, 2013CA: A Cancer Journal for Clinicians, 2013
- Cancer Trends in ChinaJapanese Journal of Clinical Oncology, 2010
- Colorectal cancer in Guangdong Province of China: A demographic and anatomic surveyWorld Journal of Gastroenterology, 2010
- Screening and early diagnosis of colorectal cancer in China: a 12 year retrospect (1994–2006)Journal of Cancer Research and Clinical Oncology, 2007
- Gene-Gene, Gene-Environment & Multiple Interactions in Colorectal CancerJournal of Environmental Science and Health, Part C, 2006
- The MAPK signalling pathways and colorectal cancerThe Lancet Oncology, 2005
- MEK5 overexpression is associated with metastatic prostate cancer, and stimulates proliferation, MMP-9 expression and invasionOncogene, 2003
- The genetic basis of colorectal cancer: Insights into critical pathways of tumorigenesisGastroenterology, 2000
- Identification of Substrates and Regulators of the Mitogen-activated Protein Kinase ERK5 Using Chimeric Protein KinasesJournal of Biological Chemistry, 1998
- Components of a New Human Protein Kinase Signal Transduction PathwayJournal of Biological Chemistry, 1995