Copy number gain and oncogenic activity of YWHAZ/14-3-3zeta in head and neck squamous cell carcinoma.
Copy number gain and oncogenic activity of YWHAZ/14-3-3zeta in head and neck squamous cell carcinoma.
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DOI：
10.1002/ijc.24346
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发表时间：
2009-08-01
影响因子：
6.4
通讯作者：
Plass C
中科院分区：
文献类型：
--
作者：
Lin M;Morrison CD;Jones S;Mohamed N;Bacher J;Plass C
基因扩增是癌症中癌基因激活的常见机制，已被用于发现新的癌基因。.低水平的拷贝数增加经常在头颈部鳞状细胞癌（HNSCC）中观察到，其中已经报道了许多扩增事件和潜在的癌基因。最近，我们应用限制性标记基因组扫描（RLGS）研究基因扩增在HNSCC和定位新的和未表征的区域在原发性肿瘤样本。染色体8q22.3（YWHAZ（14-3-3）的位置）上的增益在30-40%的HNSCC病例中被发现。从HNSCC组织微阵列上的荧光原位杂交（FISH）和免疫组化获得的数据证实了频繁的低水平YWHAZ拷贝数增加和蛋白质过表达。YWHAZ mRNA在患者的肿瘤组织中频繁上调。此外，YWHAZ RNAi显著抑制HNSCC细胞系的生长速率，并且在HaCaT永生化的人皮肤角质形成细胞中过表达YWHAZ促进过度生长以及形态学变化。降低YWHAZ水平增加G1/G 0期比例，降低S期比例和DNA合成速率。基于这些证据，我们认为YWHAZ是一个候选原癌基因，值得进一步研究其在HNSCC癌变中的作用。
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 (RLGS) 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 (14-3-3ζ), is found in 30-40% HNSCC cases. Data obtained from fluorescence in situ hybridization (FISH) 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.
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影响因子：
8
作者：
Lin, M;Smith, LT;Plass, C
通讯作者：
Plass, C
影响因子：
64.8
作者：
Di Micco, Raffaella;Fumagalli, Marzia;di Fagagna, Fabrizio d'Adda
通讯作者：
di Fagagna, Fabrizio d'Adda
影响因子：
3.7
作者：
Garnis, C;Coe, BP;Lam, WL
通讯作者：
Lam, WL
影响因子：
3.1
作者：
Jang, JS;Cho, HY;Kim, HW
通讯作者：
Kim, HW
影响因子：
10.5
作者：
Grandori, C;Wu, KJ;Mormat, RJ
通讯作者：
Mormat, RJ