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Copy number gain and oncogenic activity of YWHAZ/14‐3‐3ζ in head and neck squamous cell carcinoma
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| Zeitschriftentitel: | International Journal of Cancer |
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| Personen und Körperschaften: | , , , , , |
| In: | International Journal of Cancer, 125, 2009, 3, S. 603-611 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Wiley
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| Schlagwörter: |
| Zusammenfassung: | <jats:title>Abstract</jats:title><jats:p>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 <jats:italic>YWHAZ</jats:italic> (14‐3‐3ζ), is found in 30–40% HNSCC cases. Data obtained from fluorescence <jats:italic>in situ</jats:italic> hybridization and immunohistochemistry on HNSCC tissue microarrays confirmed frequent low‐level <jats:italic>YWHAZ</jats:italic> copy number gain and protein overexpression. <jats:italic>YWHAZ</jats:italic> mRNA was frequently upregulated in patients' tumor tissues. Furthermore, <jats:italic>YWHAZ</jats:italic> RNAi significantly suppressed the growth rate of HNSCC cell lines, and overexpression of <jats:italic>YWHAZ</jats:italic> in HaCaT immortalized human skin keratinocytes promotes overgrowth, as well as morphological changes. Reduced <jats:italic>YWHAZ</jats:italic> 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 <jats:italic>YWHAZ</jats:italic> is a candidate proto‐oncogene and deserves further investigation into its role in HNSCC carcinogenesis. © 2009 UICC</jats:p> |
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| Umfang: | 603-611 |
| ISSN: |
0020-7136
1097-0215 |
| DOI: | 10.1002/ijc.24346 |