Interruption of nuclear localization of ATBF1 during the histopathologic progression of head and neck squamous cell carcinoma

• Authors: Xiaodong Sun, Emory University; Jie Li, Emory University; Gabriel Sica, Emory University; Song-Qing Fan, Second Xiangya Hospital; Yuxiang Wang, Emory University; Zhengjia Chen, Emory University; Susan Muller, Emory University; Georgia Chen, Emory University; Xiaoying Fu, Emory University; Xueyuan Dong, Emory University; Peng Guo, Emory University; Dong M Shin, Emory University; Jin-Tang Dong, Emory University
• Journal Title: Head and Neck
• Volume: Volume 35, Number 7
• Publisher: Wiley: 12 months | 2013-07, Pages 1007-1014
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1002/hed.23077
• Subjects: Health Sciences, Oncology; Health Sciences, Pathology; Biology, Biostatistics
• Keywords: HNSCC; ATBF1; mislocalization; survival; tumor suppressor

Abstract

Background The AT-motif Binding Factor 1 (ATBF1) gene is frequently altered at the genetic level in several types of cancer, but its protein expression and subcellular localization have not been well studied in human cancers including head and neck squamous cell carcinomas (HNSCCs). Methods ATBF1 expression and localization were examined in five cell lines and 197 clinical specimens of HNSCC, and correlated with pathological and clinical characteristics. Results ATBF1 was predominantly localized in the nucleus of hyperplastic squamous epithelium. Whereas nuclear ATBF1 dramatically decreased in invasive tumors (p=0.0012), cytoplasmic ATBF1 levels progressively increased from dysplasia to invasive tumors (p<0.0001), and the increase correlated with poor survival. Reduced nuclear ATBF1 level was also detected in HNSCC cell lines. Conclusions Nuclear localization of ATBF1 is frequently interrupted in HNSCC, and the interruption is significantly associated with the progression of HNSCC. The cytoplasmic ATBF1 level could be useful for predicting patient survival.