Abstract 3304: EAPII/TTRAP is overexpressed in HNSCC

Abstract

Abstract EAPII/TTRAP, a novel protein we previously identified, was most recently recognized as the first enzyme that removes topoisomerase-mediated adducts at the 5′-phosphotyrosyl bond. EAPII/TTRAP restores 5′phosphate termini at double strand breaks preparing them for ligation. However, the physiological and pathological roles of EAPI I/TTRAP in human cells are elusive; in particular, it is unknown whether EAPII/TTRAP is involved in cancer. To determine the EAPII expression profile in the development of the Head and Neck Squamous Cell Carcinoma (HNSCC), we have developed a monoclonal antibody against EAPII suitable for immunohistochemistry (IHC). IHC was carried out in an HNSCC tissue array containing 34 cases of HNSCC and 12 peri-cancer or normal tissues. EAPII is not detectable in normal human oral squamous cells where HNSCC arises. With increased cell proliferation, weak staining of EAPII in the nucleus occurs. However, EAPII expression is significantly observed in HNSCC: Compared to 8% (1/12) in peri-cancer tissue, 82% (28/34) of HNSCC showed strong cytoplasmic-positive staining while nuclear staining reduced from 75% (9/12) to 35% (12/34). This result indicates that EAPII translocation to the cytoplasm might be an oncogenic factor that contributes to the progression of HNSCC. Consistent with the IHC study, high levels of EAPII expression are observed in many HNSCC cancer cell lines. Furthermore, lentivirus-delivered EAPII small hairpin RNA (shRNA) was employed to knockdown EAPII expression in HSNCC 686Ln-M4E cells. Cell growth curves were analyzed by SRB method. Lower cell growth was observed in the cells with reduced EAPII protein levels compared with cells infected with vector control or scramble shRNA. Altogether, our data support the hypothesis that EAPII is a potential oncogenic factor and that the elevated level of EAPII may be involved in the HNSCC development. The identification of the role of EAPII in the HNSCC development using animal models will provide further insight into the biological significance of EAPII in cancer development and progression. This work was supported in part by National Cancer Institute award 5 P50 CA128613 SPORE in Head and Neck Cancer (SYS) and Startup Fund from the Department of Hematology and Medical Oncology (RL). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3304.