Id-1 and the p65 subunit of NF-κB promote migration of nasopharyngeal carcinoma cells and are correlated with poor prognosis.
Inhibitor of differentiation (Id)-1 and nuclear factor-kappa B (NF-κB) have been detected in many malignant tumors, and their presence has been correlated with the metastatic potential of these tumors. This study was undertaken to investigate the prognostic significance of the expression of Id-1 and the p65 subunit of NF-κB (NF-κB/p65) and the proteins' roles in the invasion process of nasopharyngeal carcinoma (NPC) cells. The messenger RNA (mRNA) and protein levels of Id-1 and NF-κB/p65 in normal nasopharyngeal epithelial cells and NPC cell lines were examined using reverse transcription-PCR and western blot analysis, whereas the mRNA and protein levels of Id-1 and NF-κB/p65 in clinical NPC specimens were determined by reverse transcription-PCR and immunohistochemistry. Short hairpin RNA (shRNA) was used to silence Id-1 and NF-κB/p65 to allow for the examination of matrix metalloproteinase (MMP)-9 expression and migratory capacity changes in CNE-2 cells. Multivariate Cox analysis revealed that elevated Id-1 expression was a significant independent predictor of the 5 year overall survival rate (hazards ratio = 16.720, P = 0.005). Furthermore, elevated expression of both Id-1 and NF-κB/p65 was associated with poor clinical survival (P = 0.049). Targeting Id-1 and NF-κB/p65 mRNA with shRNA in CNE-2 cells inhibited MMP-9 expression and decreased the migratory capacity of CNE-2 cells. In conclusion, Id-1 expression is a novel independent prognostic marker molecule that helps identify NPC patients with a poor prognosis. Additionally, combined analysis of Id-1 and NF-κB/p65 can be useful for identifying patients at risk for unfavorable clinical outcomes. Id-1 or/and NF-κB/p65 enhanced tumor cell migration, which is associated with the secretion of MMP-9.
Department of Otorhinolaryngology-Head and Neck Surgery, Sun Yat-sen Memorial Hospital, Guangzhou, Public Republic of China.
Wei
W
Sun
Ming-Ming
MM
Guo
Ping
P
Han
Ji-Zhen
JZ
Lin
Fa-Ya
FY
Liang
Guang-Mou
GM
Tan
Hua-Bin
HB
Li
Musheng
M
Zeng
Xiao-Ming
XM
Huang
D001483:Base Sequence; D045744:Cell Line, Tumor; D017931:DNA Primers; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D051798:Inhibitor of Differentiation Protein 1 / Q000378:metabolism*; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism*; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; C497453:ID1 protein, human; D051798:Inhibitor of Differentiation Protein 1; D016328:NF-kappa B; D020782:Matrix Metalloproteinases