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Oncol Rep. 2012 May;27(5):1527-34. doi: 10.3892/or.2012.1669. Epub 2012 Feb 2.

NF-κB activity is downregulated by KRAS knockdown in SW620 cells via the RAS-ERK-IκBα pathway.

Author information

1
Graduate School of Education, Fujian Medical University, and Department of Medical Oncology, Union Hospital, Fuzhou, PR China.

Abstract

The relationship between KRAS and NF-κB in colorectal cancer is not clear. Western blotting was used to determine whether KRAS knockdown in SW620 cells altered the levels of NF-κB-p65 and other molecules. Furthermore, we investigated the association between the KRAS status and NF-κB expression in 167 colorectal cancers tumor tissues and their correlation with overall survival (OS) of patients with KRAS mutations and activated NF-κB. RAS, p-ERK, p-IκBα and p65 expression was decreased in SW620 cells with KRAS knockdown. The MEK inhibitor U0126 downregulated p-ERK, p-IκBα and p65 levels in SW620 cells. p65 activation in tumors with KRAS mutations was higher (50.8%) than in tumors with the wild-type KRAS gene (30.6%) (P=0.012). Compared to patients with other types of tumors, OS was lower (median 28.4 months) in patients with KRAS mutations and NF-κB activation, vs. a median of 46.3 months in patients with other types of tumors (P=0.005). NF-κB activation was reduced in SW620 cells with KRAS knockdown, possibly via the RAS-ERK-IκBα pathway. The presence of both KRAS mutations and the active form of NF-κB in CRC tumors indicates poor patient prognosis.

PMID:
22327383
DOI:
10.3892/or.2012.1669
[Indexed for MEDLINE]

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