Wnt pathway is involved in pleomorphic adenomas induced by overexpression of PLAG1 in transgenic mice
Wnt pathway is involved in pleomorphic adenomas induced by overexpression of PLAG1 in transgenic mice
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Wnt通路参与PLAG1过度表达转基因小鼠诱导的多形性腺瘤
DOI：
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发表时间：
2006
影响因子：
6.4
通讯作者：
Zhugang Wang
中科院分区：
文献类型：
--
作者：
Xu;W. Ren;Wenjun Yang;Yi Wang;Hui Kong;Long Wang;Lanzhen Yan;Guojiang Xu;J. Fei;Jiliang Fu;Chenping Zhang;Zhugang Wang
Pleomorphic adenoma gene 1 (PLAG1) was found frequently rearranged and activated in human salivary gland pleomorphic adenomas. It encodes a developmentally regulated transcription factor. Ectopic overexpression of PLAG1 has been proposed to play a crucial role in tumorigenesis of salivary gland pleomorphic adenomas. It was reported that PLAG1 can activate the transcription of insulin‐like growth factor 2 (IGF2), functioning as a protooncogene. In this report, we show that the salivary gland tumors developed in PLAG1 transgenic mice share major histopathologic features with human pleomorphic adenomas. It was found that β‐catenin, the key component of Wnt signaling pathway, was upregulated at transcriptional level in tumors developed in 3 independent transgenic mouse lines. Immunohistochemical staining revealed that expression of β‐catenin as well as c‐myc, downstream of β‐catenin in Wnt signaling pathway, was highly upregulated with overexpression of PLAG1 transgene in tumor and normal transgenic salivary gland tissues. Moreover, we found that PLAG1 can activate the transcription of mouse but not human β‐catenin in the 3T3 cells cotransfected with reporter constructs. Sequence analysis shows there are 4 PLAG1 consensus binding sites in mouse β‐catenin promoter region but not in human. Our findings provide the first in vivo evidence for the oncogenic activity of PLAG1 in pleomorphic adenoma tumorigenesis, reveal a valued animal model for human salivary gland tumors and suggest that Wnt signaling pathway may also contribute to the development of pleomorphic adenomas in transgenic mice. © 2005 Wiley‐Liss, Inc.
影响因子：
10.5
作者：
PIERCE, DF;JOHNSON, MD;MOSES, HL
通讯作者：
MOSES, HL
转基因小鼠乳腺中显性失活表皮生长因子受体的靶向表达抑制青春期乳腺导管发育。
DOI：
10.1210/mend.11.12.0019
发表时间：
1997
期刊：
Molecular endocrinology (Baltimore, Md.)
影响因子：
--
作者：
Xie,W;Paterson,AJ;Chin,E;Nabell,LM;Kudlow,JE
通讯作者：
Kudlow,JE