High expression levels of nuclear factor κB, IκB kinase α and Akt kinase in squamous cell carcinoma of the oral cavity

Nakayama, Hideki; Ikebe, Tetsuro; Beppu, Mahiro; Shirasuna, Kanemitsu

doi:10.1002/1097-0142(20011215)92:12<3037::aid-cncr10171>3.0.co;2-#

Cited by 160 publications

(106 citation statements)

References 18 publications

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“…NF-κB was localized both in the cytoplasm and in the nuclei of many malignant tumors (28,29), although in some of these, only cytoplasmic staining was observed (colorectal carcinoma) (30). In addition, the percentage of nuclear NF-κB also varied from only 5.6% of cells in oral squamous carcinoma (31,32) to more than 30% in prostate carcinoma (24), which is similar to ours and other studies (33).…”

Section: Discussionsupporting

confidence: 89%

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Relationship Between Vascular Endothelial Growth Factor and Nuclear Factor-κB in Renal Cell Tumors

et al. 2008

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Aim To assess the relationship between protein and messenger RNA (mRNA) levels of vascular endothelial growth factor (VEGF) and subcellular localization of nuclear factor-kappa B (NF-κB), proliferation rate of tumor cells, and clinicopathological characteristics of renal cell tumors.Methods We analyzed 31 one renal cell tumors -22 clear cell renal cell carcinomas (CCRCC) and 9 other histologic types (non-CCRCC). VEGF expression and subcellular localization of p65 member of NF-κB and Ki67 were immunohistochemically evaluated for the proliferation rate of tumor cells. Expression of VEGF mRNA was assessed using quantitative real-time polymerase chain reaction after total RNA extraction from snap-frozen tumor tissue samples.Results Cytoplasmic localization of VEGF protein in renal cell tumors showed a perimembranous and diffuse pattern, the former being more evident in CCRCC (27.1 ± 18.9 vs 3.3 ± 10 % tumors, P<0.001) and the latter in non-CCRCC type (71.7 ± 23.2 vs 31.1 ± 22.1 % tumors, P < 0.001). Heterogeneity in VEGF gene expression was more pronounced in CCRCC type than in non-CCRCC type (P = 0.004). In addition, perimembranous VEGF pattern was associated with higher VEGF mRNA levels (P = 0.006) and diffuse VEGF pattern with lower VEGF mRNA levels (P < 0.001). Nuclear and cytoplasmic staining of NF-κB/ p65 was observed in the majority of tumor cells. A significant association was recorded between cytoplasmic NK-κB/65 staining and VEGF staining of diffuse pattern (P = 0.026). Association between NF-κB/65 and proliferation rate of tumor cells was significant for cytoplasmic staining (P = 0.039) but not for nuclear NFkB/p65 staining (P = 0.099). ConclusionHigher but inhomogeneous expression of VEGF in tumor cells, especially in CCRCCs, is associated with NF-κB/65 activity. This indicates that both VEGF and NF-κB/65 may be important in renal carcinogenesis, representing a possible molecular target in the treatment of renal cell carcinoma.

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Section: Discussionsupporting

confidence: 89%

“…The functional significance of this protein in the cytoplasm should be further explored. Nonetheless, the hypothesis of Nakayama et al (31) that the presence of a large amount of NF-κB in the cytoplasm may easily result in the activation of NF-κB, even by faint stimulation, seems quite reasonable.…”

Section: Discussionmentioning

confidence: 99%

Relationship Between Vascular Endothelial Growth Factor and Nuclear Factor-κB in Renal Cell Tumors

et al. 2008

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“…Activation of NFkB has been implicated in the development and progression of OSCC. 26 We have defined in the present study that ANE can activate JNK and NF-kB in oral keratinocytes.…”

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confidence: 73%

Areca (betel) nut extract activates mitogen‐activated protein kinasesand NF‐κB in oral keratinocytes

Lin

Lee

et al. 2005

Intl Journal of Cancer

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Areca (betel) was recently proved a carcinogenic substance by the International Agency for Research on Cancer. However, the signaling impact of areca in oral keratinocyte is still obscure. Mitogen‐activated protein kinase superfamilies, including extracellular signal‐regulated kinase (ERK), c‐Jun N‐terminal kinases (JNK) and p38, together with transcription factor NF‐κB, are important signaling elements. We examined the activation of these signaling pathways in OECM‐1 and SAS oral keratinocytes, treated with ripe areca nut extract (ANE). In both cells, a rapid increase in JNK1 activity at 0.5 hr was noted following treatment of ANE. ERK was profoundly activated during 0.5–2 hr in OECM‐1 cells. Contrasting p38 activity was noted in these 2 cells. In both cells, ANE also activated NF‐κB pathway in a biphasic manner, particularly for SAS cells. NF‐κB was activated by ∼ 2‐ to 4‐fold at 0.5–1 hr and a plateau or slight decrease of activity existed between 1 and 6 hr. Later, another higher episode of NF‐κB activity was raised. This was accompanied with the rapid degradation in cytosolic IκBα as well as an increase of nuclear NF‐κB in both cells. ANE treatment did not activate epidermal growth factor receptor signaling system, but blockage of NF‐κB activation rendered the suppression of ANE‐modulated COX‐2 upregulation in OECM‐1. This study identified that ANE affected interactive signaling systems in oral keratonocytes that could be the pathogenetic basis for areca. © 2005 Wiley‐Liss, Inc.

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“…Overall survival dependent on cytoplasmic (C and E) and nuclear (D and F) RelA overexpression for the whole study cohort (C and D) as well as for the subgroup of node-negative patients (E and F). Sweeney et al, 2004), endometrial (Pallares et al, 2004), hepatocellular (Tai et al, 2000) and oral (Nakayama et al, 2001) as well as cervical (Nair et al, 2003) carcinoma. Reports on RelA expression in pancreatic cancer are sparse.…”

Section: Discussionmentioning

confidence: 99%

High expression of RelA/p65 is associated with activation of nuclear factor-κB-dependent signaling in pancreatic cancer and marks a patient population with poor prognosis

et al. 2007

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Activation of nuclear factor-kB (NF-kB) signaling was observed in pancreatic adenocarcinoma cell lines and tumours. However, information on the expression of RelA/p65, the major transcription activating NF-kB subunit, in these carcinomas and possible correlations thereof with NF-kB activation and patient survival is not available. To provide this missing translational link, we analysed expression of RelA/p65 in 82 pancreatic adenocarcinomas by immunohistochemistry. Moreover, we measured activation of the NF-kB pathway in 11 tumours by quantitative PCR for NF-kB target genes. We observed strong cytoplasmic or nuclear expression of RelA/p65 in 42 and 37 carcinomas, respectively. High cytoplasmic and nuclear expression of RelA/p65 had negative prognostic impact with 2-year survival rates for patients without cytoplasmic or nuclear RelA/p65 positivity of 41 and 40% and rates for patients with strong cytoplasmic or nuclear RelA/p65 expression of 22 and 20%, respectively. High RelA/p65 expression was correlated to increased expression of NF-kB target genes. The observation that high expression of RelA/p65 is correlated to an activation of the NF-kB pathway and indicates poor patient survival identifies a patient subgroup that might particularly benefit from NF-kB-inhibiting agents in the treatment of pancreatic cancer. Based on our findings, this subgroup could be identified by applying simple immunohistochemical techniques.

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High expression levels of nuclear factor κB, IκB kinase α and Akt kinase in squamous cell carcinoma of the oral cavity

Cited by 160 publications

References 18 publications

Relationship Between Vascular Endothelial Growth Factor and Nuclear Factor-κB in Renal Cell Tumors

Relationship Between Vascular Endothelial Growth Factor and Nuclear Factor-κB in Renal Cell Tumors

Areca (betel) nut extract activates mitogen‐activated protein kinasesand NF‐κB in oral keratinocytes

High expression of RelA/p65 is associated with activation of nuclear factor-κB-dependent signaling in pancreatic cancer and marks a patient population with poor prognosis

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