Nox1 is over-expressed in human colon cancers and correlates with activating mutations in K-Ras
| Autor: | Wenhui Liu, Sylvie Robine, Eunice Laurent, Roberto A. Macina, Guangjie Cheng, J. David Lambeth, Jackie Papkoff, James McCoy |
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| Rok vydání: | 2008 |
| Předmět: |
Adult
Male Cancer Research Pathology medicine.medical_specialty Angiogenesis Colorectal cancer Fluorescent Antibody Technique Mice Transgenic Biology medicine.disease_cause Article Mice medicine Animals Humans Large intestine RNA Messenger Aged Aged 80 and over Messenger RNA Mutation NADPH Oxidases Cancer Middle Aged medicine.disease Immunohistochemistry Up-Regulation Gene Expression Regulation Neoplastic Genes ras medicine.anatomical_structure Oncology Apoptosis Colonic Neoplasms NADPH Oxidase 1 cardiovascular system Cancer research Female Tumor Suppressor Protein p53 |
| Zdroj: | International Journal of Cancer. 123:100-107 |
| ISSN: | 1097-0215 0020-7136 |
| DOI: | 10.1002/ijc.23423 |
| Popis: | The NADPH-oxidase 1 (Nox1) is a homolog of gp91phox, the catalytic subunit of the phagocyte superoxide-generating NADPH-oxidase. Nox1 is expressed in normal colon epithelial cells and in colon tumor cell lines, and overexpression in model cells has been implicated in stimulation of mitogenesis and angiogenesis and inhibition of apoptosis. This suggests that aberrant expression of Nox1 could contribute to the development of colorectal cancer. Herein, we examine the expression of Nox1 mRNA in 24 colon tumors of various stages compared with paired adjacent normal tissue from the same patient, and correlate expression with some common mutations associated with colon cancer. Nox1 was overexpressed compared with paired normal tissue in 57% of tumors as early as the adenoma stage, with no correlation of expression level with tumor stage. Overexpression of Nox1 mRNA correlated with Nox1 protein levels assessed by immunofluorescence and immunohistochemistry with an antibody specific for Nox1. There was a strong correlation between Nox1 mRNA level and activating mutations in codons 12 and 13 of K-Ras. Eighty percent (8/10) of tumors with codons 12 and 13 mutations had a 2-fold or more increase in Nox1 mRNA, and 70% (7/10) had a 5-fold or greater increase. Transgenic mice expressing K-Ras(G12V) in the intestinal epithelium also expressed markedly elevated Nox1 in both small and large intestine. There was no correlation between inactivating mutations in the tumor suppressor p53 and Nox1 expression. We conclude that Nox1 mRNA and protein are overexpressed in colon cancer and are strongly correlated with activating mutations in K-Ras. |
| Databáze: | OpenAIRE |
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