The phosphorylation status of merlin in sporadic vestibular Schwannomas.
The events leading to Schwannomas development are still largely unknown. Some studies have demonstrated that merlin acts as a tumor suppressor by blocking Ras-mediated signaling. In this study, we analyze the clinical and biological behaviors of seven randomly selected sporadic vestibular Schwannomas removed from the patients. We find that merlin was commonly lost in these Schwannomas, due to loss of merlin expression or phosphorylation status of merlin expression. Heightened CDKs/cyclins signal transduction concomitant with loss of p27 was well correlated with loss of functional merlin in Schwannomas. More, we show that phosphorylated merlin Schwannomas exhibited increased Ras/Rac/PAK signal transduction. That was in agreement with the severe clinical behaviors, i.e., phosphorylation status of merlin increased tumor size in sporadic vestibular Schwannomas. These results led us to suggest that phosphorylated merlin, a kind of type of mutation merlin, is involved in tumorigenesis of sporadic vestibular Schwannomas.
Wang
Zhaoyan
Z
Department of Otolaryngology-Head & Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai, 200092, China.
Lu
Yanjun
Y
Tang
Juanjuan
J
Wang
Haojie
H
Wu
Hao
H
D000328:Adult; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000172:deficiency; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D025581:Neurofibromin 2 / Q000032:analysis / Q000378:metabolism*; D009464:Neuroma, Acoustic / Q000737:chemistry* / Q000209:etiology / Q000473:pathology; D010766:Phosphorylation; D015398:Signal Transduction; D047368:Tumor Burden; D055815:Young Adult; D018631:ras Proteins / Q000378:metabolism
D016213:Cyclins; D025581:Neurofibromin 2; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases; D018631:ras Proteins