Epstein-Barr virus encoded latent membrane protein-1 induces epithelial cell proliferation and sensitizes transgenic mice to chemical carcinogenesis.
Epstein-Barr virus encoded latent membrane protein-1 induces epithelial cell proliferation and sensitizes transgenic mice to chemical carcinogenesis.
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Epstein-Barr 病毒编码的潜伏膜蛋白 1 诱导上皮细胞增殖并使转基因小鼠对化学致癌作用敏感。
作者：
John A. Curran;Fiona S. Laverty;D. Campbell;Jennifer Macdiarmid;Joanna B. Wilson
发现EBV与100%的低分化或未分化的鼻咽癌（一种上皮起源的肿瘤）相关。EB病毒潜伏膜蛋白1（LMP 1）可能在该病的发生发展中起一定的作用。这里开始的实验被设计成检查体内的活性LMP 1在表皮的PyLMP 1转基因小鼠在其致癌作用的推定作用。与对照组相比，转基因阳性表皮显示有丝分裂指数增加2-3倍，同时增殖性细胞角蛋白标记物（K6和K14）的表达水平增加。这些结果提供了直接的证据，LMP 1诱导增殖，否则正常上皮细胞在体内。为了评估LMP 1在致瘤进展中的作用，用化学致癌物局部处理转基因小鼠。PyLMP 1小鼠对化学致癌物高度敏感，比对照组以更快的速度发展出更多的小乳头状瘤。此外，LMP 1可以替代12-O-十四烷酰基佛波醇-13-乙酸酯治疗肿瘤促进。然而，LMP 1抑制良性病变的扩展，并没有促进病变发展为癌或这些发展为更恶性的梭形细胞癌。这些数据表明，在致癌过程的早期，LMP 1在化学引发后充当肿瘤促进剂;但是，矛盾的是，它也可能对病变的扩展或进展引入障碍。
EBV is found to be associated with 100% of poorly or undifferentiated nasopharyngeal carcinomas, a tumor of epithelial origin. The latent membrane protein-1 (LMP1) of EBV, may play a causal role in the development of this disease. The experiments initiated here were designed to examine the activity of LMP1 in vivo in the epidermis of PyLMP1 transgenic mice in relation to its putative role in carcinogenesis. Transgenic positive epidermis showed a 2-3-fold increase in the mitotic index, coupled with an increased level of expression of proliferative cytokeratin markers (K6 and K14) over controls. These results provide direct evidence that LMP1 induces proliferation in otherwise normal epithelial cells in vivo. To assess the role of LMP1 in tumorigenic progression, transgenic mice were treated topically with chemical carcinogens. PyLMP1 mice were highly sensitive to chemical carcinogens, developing significantly more small papillomas at a faster rate than controls. Furthermore, LMP1 could substitute for 12-O-tetradecanoylphorbol-13-acetate treatment in tumor promotion. However, LMP1 inhibited expansion of the benign lesions and did not enhance progression of the lesions to carcinomas or the progression of these to the more malignant spindle cell carcinomas. These data demonstrate that, early in the carcinogenic process, LMP1 acts as a tumor promoter after chemical initiation; but, paradoxically, it may also introduce a hurdle against expansion or progression of a lesion.
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不同化学致癌方案产生的小鼠皮肤癌的转移潜力。
DOI：
--
发表时间：
1991
期刊：
Invasion & metastasis
影响因子：
--
作者：
Chiba,M;Aldaz,CM;Conti,CJ;Klein-Szanto,AJ
通讯作者：
Klein-Szanto,AJ
影响因子：
11.2
作者：
D. Greenhalgh;Xiaojing Wang;L. Donehower;D. Roop
通讯作者：
D. Greenhalgh;Xiaojing Wang;L. Donehower;D. Roop
影响因子：
8
作者：
L. Hu;Fu Chen;Xi Zheng;I. Ernberg;S. Cao;B. Christensson;G. Klein;G. Winberg
通讯作者：
L. Hu;Fu Chen;Xi Zheng;I. Ernberg;S. Cao;B. Christensson;G. Klein;G. Winberg
人角蛋白 1 的分化特异性表达由复合 AP-1/类固醇激素元件介导。
DOI：
--
发表时间：
1994
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Lu,B;Rothnagel,JA;Longley,MA;Tsai,SY;Roop,DR
通讯作者：
Roop,DR
DOI：
10.1016/s0021-9258(18)35741-7
发表时间：
1992-12
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
C. D. Laherty;Hong-Ming Hu;A. Opipari;F. Wang;V. Dixit
通讯作者：
C. D. Laherty;Hong-Ming Hu;A. Opipari;F. Wang;V. Dixit