Stage-associated dynamic activity profile of transcription factors in nasopharyngeal carcinoma progression based on protein/DNA array analysis.
Transcription factors (TFs) are crucial modulators of gene regulation during the development and progression of tumors. We previously reported the activation of TFs in nasopharyngeal carcinoma (NPC) cell lines. In this study, we explored the activity profiles of TFs in Protein/DNA array data of a 12-tissue independent set and a 13-tissue pooled set of NPC that included different clinical stages. TFs associated with tumor progression were revealed using a generalized linear model-based regression analysis. Immunohistochemical analysis of clinical NPC samples was used to validate the results of array analysis. We identified 26 TFs that showed increased activities. Of these 26 TFs, 16 were correlated with clinical stages. Activity changes of AP2 and ATF/CREB were confirmed by electrophoretic mobility shift assay (EMSA), and increased expression of AP2α, β, γ, ATF2, and ATF1 in nuclei of tumor cells was associated with clinical stages. In addition, the expressions of AP2α, ATF2, and ATF1 were correlated with those of their target genes (epithelia growth factor receptor (EGFR) and matrix metalloproteinase 2 (MMP-2), respectively). This study provides data and valuable clues that can be used to further investigate the laws of gene transcription regulation in NPC and to identify suitable targets for the development of TF-targeted antitumor agents.
Su
Bo
B
Cancer Research Institute, Central South University, Changsha, Hunan, People's Republic of China.
Tang
Hai-Lin
HL
Deng
Min
M
Liao
Qian-Jin
QJ
Zeng
Xi
X
Zhang
Wen-Ling
WL
Xiang
Bo
B
Wang
Li
L
Li
Xiao-Ling
XL
Li
Xia-Yu
XY
Wu
Ming-Hua
MH
Li
Gui-Yuan
GY
D001483:Base Sequence; D015153:Blotting, Western; D015342:DNA Probes; D018450:Disease Progression; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000378:metabolism*
D015342:DNA Probes; D009363:Neoplasm Proteins; D014157:Transcription Factors