Altered expression of transforming growth factor betas during urethral and bulbourethral gland tumor progression in transgenic mice carrying the androgen-responsive C3(1) 5' flanking region fused to SV40 large T antigen.
Altered expression of transforming growth factor betas during urethral and bulbourethral gland tumor progression in transgenic mice carrying the androgen-responsive C3(1) 5' flanking region fused to SV40 large T antigen.
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在携带与 SV40 大 T 抗原融合的雄激素反应性 C3(1) 5 侧翼区的转基因小鼠的尿道和尿道球腺肿瘤进展过程中，转化生长因子 β 的表达发生改变。
作者：
M. Shibata;C. Jorcyk;D. Devor;K. Yoshidome;S. Rulong;J. Resau;N. Roche;A. Roberts;J. Ward;J. Green
我们证明，SV40大T抗原（TAg）向尿道（尿道周围）和尿道球腺上皮的靶向表达会导致7个月后这些组织中腺癌的形成，这是人类自发肿瘤形成的极其罕见的部位。可以预见，尿道腺中增殖性病变的发展遵循一个时间过程，大约三分之一的雄性动物在一岁时会出现尿道肿瘤。这些器官中的肿瘤进展与 TAg 和 p53 表达水平相关。免疫沉淀证实SV40 TAg蛋白在体内与p53和Rb p110结合。在尿道腺癌的肿瘤进展过程中评估了转化生长因子β（TGFbetas）的表达。在肿瘤前期和肿瘤病变中发现细胞内和细胞外 TGFβ1 和细胞外 TGFβ3 升高，表明 TGFβ 增加可能会促进肿瘤生长。 c-Met表达在尿道腺癌中表现出表达增加的趋势。我们推测激素反应性 C3(1) 基因定向表达 SV40 TAg 以及随后这些器官中肿瘤的形成受到雄激素的影响，因为这些组织和癌表达雄激素受体 (AR) 并且仅出现在雄性转基因小鼠中。从尿道癌建立的几种细胞系也显示出表达 AR，但在培养中不依赖于雄激素。据我们所知，这是第一个针对尿道癌和尿道球癌的转基因动物模型。这种转基因小鼠模型和源自它的细胞系可能为剖析这些器官肿瘤发生的分子机制提供了独特的机会，否则这些器官很少会发展成癌症。
We demonstrate that targeted expression of SV40 large T antigen (TAg) to the urethral (periurethral) and bulbourethral gland epithelium leads to adenocarcinoma formation in these tissues after 7 months of age, which are extremely rare sites for spontaneous tumor formation in humans. The development of proliferative lesions in the urethral gland predictably follows a temporal course of progression with approximately one third of male animals developing urethral tumors by 1 year of age. Tumor progression in these organs correlates to the level of TAg and p53 expression. Immunoprecipitation confirmed that SV40 TAg protein was bound to p53 and Rb p110 in vivo. Expression of transforming growth factor beta (TGFbetas) was evaluated during tumor progression of urethral gland carcinomas. Elevations of intracellular and extracellular TGFbeta1 and extracellular TGFbeta3 were found in preneoplastic and neoplastic lesions, suggesting that increased TGFbetas may augment tumor growth. c-Met expression showed a tendency for increased expression in the urethral gland carcinomas. We speculate that the directed expression of SV40 TAg by the hormone responsive C3(1) gene and subsequent tumor formation in these organs is influenced by androgens, since these tissues and carcinomas express androgen receptor (AR) and arise only in male transgenic mice. Several cell lines established from the urethral carcinomas were also shown to express AR, but are not androgen dependent in culture. To our knowledge, this is the first transgenic animal model for urethral and bulbourethral carcinomas. This transgenic mouse model and the cell lines derived from it may provide a unique opportunity for dissecting molecular mechanisms involved in the tumorigenesis of these organs which otherwise rarely develop cancer.
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DOI：
10.1073/pnas.93.26.15152
发表时间：
1996-12-24
影响因子：
11.1
作者：
Zhau, HYE;Chang, SM;Chung, LWK
通讯作者：
Chung, LWK
转化生长因子-β 1 和 β 3 mRNA 水平升高与重建小鼠前列腺中 ras myc 诱导的癌症相关：进展过程中旁分泌作用的证据。
DOI：
10.1210/mend-5-4-503
发表时间：
1991
期刊：
Molecular endocrinology (Baltimore, Md.)
影响因子：
--
作者：
Merz,VW;Miller,GJ;Krebs,T;Timme,TL;Kadmon,D;Park,SH;Egawa,S;Scardino,PT;Thompson,TC
通讯作者：
Thompson,TC
转化生长因子β1在体外刺激转移性和原发性小鼠前列腺癌衍生细胞系的对比反应。
DOI：
--
发表时间：
1996
期刊：
Cancer research.
影响因子：
--
作者：
Sehgal,I;Baley,PA;Thompson,TC
通讯作者：
Thompson,TC
影响因子：
6.6
作者：
Pisters, LL;ElNaggar, AK;Lin, SH
通讯作者：
Lin, SH