caa a22 4500 606183655 CHVBK 20210128100822.0 cr unu---uuuuu 210128e20150901xx s 000 0 eng 10.1007/s00405-014-3135-y doi (NATIONALLICENCE)springer-10.1007/s00405-014-3135-y P14ARF deficiency and its correlation with overexpression of p53/MDM2 in sporadic vestibular schwannomas [Elektronische Daten] [Ying Chen, Zhao-yan Wang, Hao Wu] Recent studies have shed considerable light into schwannomas. To date, only merlin has been identified as a hallmark or pathogenesis of both sporadic and NF2-related schwannomas. Here, we show, by immunoblot and immunohistochemical analyses of 58 sporadic vestibular schwannomas, that upregulation of p53 was observed in 90% of tumors examined. No p53 mutations were found in 12% tumors analyzed. Expression of p14ARF was negative in 95% of tumors, while overexpression of MDM2 was found in all specimens. Aberrant DNA hypermethylation of the p14ARF promoter was observed in three of seven tumors examined (43%), associated with remarkably decreased mRNA levels. The very high degree of concordance in the aberrations of the p14ARF/MDM2/p53 pathway in this tumor may be considered to be a new player in the pathogenesis of sporadic vestibular schwannomas. Moreover, expression of p21 (waf1) was negative in all tumors, suggesting that the aberration of this pathway is associated with greater attenuation of p21-mediated signals that are critical for growth inhibition. These data are in agreement with the model in RT-4 rat schwannoma cells: i.e., overexpression of ARF was associated with accumulation of p21 expression both at protein and mRNA levels. ShRNA knock-down of p53 expression attenuated p21-mediated increase in cellular arrest in the G1-phase, suggesting that p14ARF regulates p21 protein levels through a p53-dependent pathway. Thus, this study reveals a high degree of concordance in the aberrations of the p14ARF/MDM2/p53 pathway with the development of sporadic vestibular schwannomas. Springer-Verlag Berlin Heidelberg, 2014 p14ARF nationallicence p53 nationallicence MDM2 nationallicence p21 (waf1) nationallicence Sporadic vestibular schwannomas nationallicence Chen Ying Department of Otolaryngology, Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Kongjiang Road #1665, 200092, Shanghai, China aut Wang Zhao-yan Department of Otolaryngology, Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Kongjiang Road #1665, 200092, Shanghai, China aut Wu Hao Department of Otolaryngology, Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Kongjiang Road #1665, 200092, Shanghai, China aut European Archives of Oto-Rhino-Laryngology Springer Berlin Heidelberg 272/9(2015-09-01), 2227-2234 0937-4477 272:9<2227 2015 272 405 https://doi.org/10.1007/s00405-014-3135-y text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00405-014-3135-y text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Chen Ying Department of Otolaryngology, Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Kongjiang Road #1665, 200092, Shanghai, China aut NATIONALLICENCE 700 1- Wang Zhao-yan Department of Otolaryngology, Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Kongjiang Road #1665, 200092, Shanghai, China aut NATIONALLICENCE 700 1- Wu Hao Department of Otolaryngology, Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Kongjiang Road #1665, 200092, Shanghai, China aut NATIONALLICENCE 773 0- European Archives of Oto-Rhino-Laryngology Springer Berlin Heidelberg 272/9(2015-09-01), 2227-2234 0937-4477 272:9<2227 2015 272 405