NF-κB activity is downregulated by KRAS knockdown in SW620 cells via             the RAS-ERK-IκBα pathway.
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.
Graduate School of Education, Fujian Medical University, and Department of Medical Oncology, Union Hospital, Fuzhou, PR China.
Gen
G
Lin
Zhiwei
Z
Tang
Yun-Bin
YB
Ye
Qiang
Q
Chen
D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality; D015536:Down-Regulation; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D020868:Gene Silencing; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism*; D009154:Mutation; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D009367:Neoplasm Staging; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras); D034741:RNA, Small Interfering; D015398:Signal Transduction; D018631:ras Proteins / Q000235:genetics* / Q000378:metabolism
D020672:I-kappa B Proteins; C117307:KRAS protein, human; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D000072000:NF-KappaB Inhibitor alpha; D048049:Extracellular Signal-Regulated MAP Kinases; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins