title: Copy number gain and oncogenic activity of YWHAZ/14-3-3zeta in head and neck squamous cell carcinoma.
abstract: Gene amplification, a common mechanism for oncogene activation in cancers, has been used in the discovery of novel oncogenes. Low-level copy number gains are frequently observed in head and neck squamous cell carcinomas (HNSCCs) where numerous amplification events and potential oncogenes have already been reported. Recently, we applied restriction landmark genome scanning to study gene amplifications in HNSCC and located novel and uncharacterized regions in primary tumor samples. Gain on chromosome 8q22.3, the location of YWHAZ (14-3-3zeta), is found in 30-40% HNSCC cases. Data obtained from fluorescence in situ hybridization and immunohistochemistry on HNSCC tissue microarrays confirmed frequent low-level YWHAZ copy number gain and protein overexpression. YWHAZ mRNA was frequently upregulated in patients' tumor tissues. Furthermore, YWHAZ RNAi significantly suppressed the growth rate of HNSCC cell lines, and overexpression of YWHAZ in HaCaT immortalized human skin keratinocytes promotes overgrowth, as well as morphological changes. Reduced YWHAZ levels increased the G1/G0-phase proportion, decreased the S-phase proportion and the rate of DNA synthesis. Based on this evidence, we suggest that YWHAZ is a candidate proto-oncogene and deserves further investigation into its role in HNSCC carcinogenesis.
authors.affiliation: Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University Medical Center, Columbus, OH, USA.
authors.forename: Mauting
authors.initials: M
authors.lastname: Lin
authors.forename: Carl D
authors.initials: CD
authors.lastname: Morrison
authors.forename: Susie
authors.initials: S
authors.lastname: Jones
authors.forename: Nehad
authors.initials: N
authors.lastname: Mohamed
authors.forename: Jason
authors.initials: J
authors.lastname: Bacher
authors.forename: Christoph
authors.initials: C
authors.lastname: Plass
mesh_terms: D048948:14-3-3 Proteins; D000328:Adult; D000368:Aged; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D004273:DNA, Neoplasm / Q000378:metabolism; D005260:Female; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D018832:Molecular Chaperones / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: D048948:14-3-3 Proteins; D004273:DNA, Neoplasm; C000715470:MAS1 protein, human; D018832:Molecular Chaperones; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C490391:Ywhaz protein, rat