Abstract 4004: Mislocalization of ATBF1 is associated with progression of head and neck squamous cell carcinoma

Abstract

Abstract Purpose: In prostate, breast and gastric cancers, the nuclear protein AT-motif Binding Factor 1 (ATBF1) undergoes frequent reduced mRNA expression and genomic alterations. However, the protein level and subcellular localization of ATBF1 have not been well studied in human cancers. In the present study, we examined ATBF1 expression, localization and function in head and neck squamous cell carcinomas (HNSCCs). Experimental Design: ATBF1 expression and localization were examined by immunohistochemistry in a series of 197 surgically dissected HNSCC specimens and correlated with clinical outcomes. In addition, ATBF1 expression was characterized in five HNSCC cell lines. We then mutated the nuclear localization signal (NLS) of ATBF1 and studied the effects of cytoplasmic versus nuclear ATBF1 on the growth kinetics of the 212LN cell line. Results: ATBF1 had a predominantly nuclear localization in hyperplastic squamous epithelium, and nuclear ATBF1 dramatically decreased in invasive tumors. Conversely, cytoplasmic ATBF1 levels progressively increased from dysplasia to invasive tumors. Cytoplasmic ATBF1 levels were significantly inversely correlated with overall survival and disease free survival. Similar expression patterns and subcellular localization of ATBF1 were observed in HNSCC cell lines. In order to better define the role of subcellular localization of ATBF1, we identified and mutated its nuclear localization signal (NLS). Mutation of the NLS converted the inhibitory effect of ATBF1 on cell growth to growth-promoting. Conclusions: Aberrant cytoplasmic localization of ATBF1 is significantly associated progression of HNSCC, and cytoplasmic ATBF1 may be a potential biomarker for its early detection. Our results suggest that nuclear ATBF1 functions as a tumor suppressor in head and neck squamous epithelial cells and that this tumor suppressor effect is sequestered by cytoplasmic localization during HNSCC progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4004. doi:10.1158/1538-7445.AM2011-4004