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Zana K. Ahmad, BS; Xabier Altuna, MD; Jay Patrick Lopez, BA; Yi An, BS; Jessica Wang-Rodriguez, MD; Vikram R. Juneja; Jocelyn S. Chen, BS; Maria Jesus Arandazi, MD; Joseph Aguilera, BS; Jeffrey P. Harris, MD, PhD; Weg M. Ongkeko, MD, PhD

Arch Otolaryngol Head Neck Surg. 2009;135(7):662-669.

Objectives  To determine the expression of the p53 family member p73 in vestibular schwannoma (VS) and to determine the potential role of this tumor suppressor in regulating the proliferation of HEI193, a human papillomavirus E6-E7 immortalized VS cell line.

Methods  Immunohistochemical staining was used to investigate the expression of p73 in 34 cases of archived VS tissue, while Western blot analysis and immunofluorescence were performed to demonstrate the expression and localization of p73 in HEI193. After transfection of a full-length p73 plasmid (TAp73), flow cytometry analysis was performed to determine the effect of p73 expression on cell cycle distribution, while annexin V–FITC (fluorescein isothiocyanate) analysis and TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling) assay were used to measure apoptosis. The effect of p73 expression on ionizing radiation–induced cell death was also investigated with annexin V staining, TUNEL assay, and flow cytometry analysis.

Results  Of the 34 vestibular schwannoma tissues examined, p73 was expressed in 14 (41%) but was not expressed in HEI193. Transfection of p73 alone resulted in increased apoptosis and necrosis, and G₁ accumulation with concomitant induction of p21. The presence of p73 also significantly increased early apoptosis (P = .046), late apoptosis (P < .001), and necrosis (P = .009) on exposure of the HEI193 cells to ionizing radiation.

Conclusion  Forced expression of p73, perhaps by gene therapy, to induce apoptosis directly or to sensitize VS tumors to ionizing radiation may have relevant therapeutic applications.

Author Affiliations: Division of Otolaryngology–Head and Neck Surgery, Department of Surgery (Messrs Ahmad, Lopez, An, and Juneja, Ms Chen, and Drs Harris and Ongkeko), Department of Pathology (Dr Wang-Rodriguez), and Division of Radiation Oncology, Department of Radiology (Mr Aguilera), University of California, San Diego; Servicio de Otorrinolaringología (Dr Altuna) and Servicio de Pathología (Dr Arandazi), Hospital Donosita, San Sebastian, Spain; and Department of Veterans Affairs San Diego Healthcare System, San Diego (Dr Wang-Rodriguez).

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