Down-regulation of transforming growth factor-beta type II receptor (TGF-betaRII) protein and mRNA expression in cervical cancer.
Down-regulation of transforming growth factor-beta type II receptor (TGF-betaRII) protein and mRNA expression in cervical cancer.
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DOI：
10.1186/1476-4598-7-3
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发表时间：
2008-01-09
期刊：
影响因子：
37.3
通讯作者：
Gariglio P
中科院分区：
文献类型：
--
作者：
Diaz-Chavez J;Hernandez-Pando R;Lambert PF;Gariglio P
宫颈癌的发生是一个由“高危”人乳头瘤病毒（HR-HPV）（最常见的是HPV 16）启动的多步骤过程。然而，感染本身并不足以诱发恶变。转化生长因子β（Transforming growth Factor β，TGF-β）抑制上皮细胞增殖，TGF-β及其受体表达的改变可能在肿瘤发生中起重要作用。宫颈癌中启动肿瘤形成的一个辅助因素是长期暴露于性激素。有趣的是，先前的研究表明雌激素抑制TGF-β诱导的基因表达。为了检测TGF-β2、TGF-βRII、p15和c-myc的表达，我们采用原位RT-PCR、实时PCR和免疫组织化学方法，在人角蛋白14启动子控制下表达HPV 16癌基因E7的转基因小鼠（K14-E7转基因小鼠）和非转基因对照小鼠中，用17β-雌二醇缓释丸治疗6个月。雌激素诱导的癌变伴随着K14-E7小鼠宫颈和阴道鳞状上皮内增殖细胞的发生率和分布增加。与非转基因小鼠相比，K14-E7转基因小鼠中TGF-β2 mRNA和蛋白水平增加，并且在非转基因和转基因小鼠中，在去乙酰化处理后进一步增加。相反，与非转基因小鼠相比，K14-E7转基因小鼠中TGF-βRII mRNA和蛋白水平降低，并且在转基因小鼠中激素处理后这些水平进一步降低。我们还观察到，c-myc mRNA水平在K14-E7小鼠高，无论雌激素治疗和雌激素治疗的非转基因小鼠增加。最后，我们发现K14-E7小鼠中p15 mRNA水平没有增加。这些结果表明，雌激素和E7在诱导宫颈癌中的协同作用可能部分反映了两种因子调节TGF-β信号转导的能力。
Cervical carcinogenesis is a multistep process initiated by "high risk" human papillomaviruses (HR-HPV), most commonly HPV16. The infection per se is, however, not sufficient to induce malignant conversion. Transforming Growth Factor β (TGF-β) inhibits epithelial proliferation and altered expression of TGF-β or its receptors may be important in carcinogenesis. One cofactor candidate to initiate neoplasia in cervical cancer is the prolonged exposure to sex hormones. Interestingly, previous studies demonstrated that estrogens suppress TGF-β induced gene expression. To examine the expression of TGF-β2, TGF-βRII, p15 and c-myc we used in situ RT-PCR, real-time PCR and immunohistochemistry in transgenic mice expressing the oncogene E7 of HPV16 under control of the human Keratin-14 promoter (K14-E7 transgenic mice) and nontransgenic control mice treated for 6 months with slow release pellets of 17β-estradiol. Estrogen-induced carcinogenesis was accompanied by an increase in the incidence and distribution of proliferating cells solely within the cervical and vaginal squamous epithelium of K14-E7 mice. TGF-β2 mRNA and protein levels increased in K14-E7 transgenic mice as compared with nontransgenic mice and further increased after hormone-treatment in both nontransgenic and transgenic mice. In contrast, TGF-βRII mRNA and protein levels were decreased in K14-E7 transgenic mice compared to nontransgenic mice and these levels were further decreased after hormone treatment in transgenic mice. We also observed that c-myc mRNA levels were high in K14-E7 mice irrespective of estrogen treatment and were increased in estrogen-treated nontransgenic mice. Finally we found that p15 mRNA levels were not increased in K14-E7 mice. These results suggest that the synergy between estrogen and E7 in inducing cervical cancer may in part reflect the ability of both factors to modulate TGF-β signal transduction.
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影响因子：
13
作者：
Markowitz, Sanford D.;Roberts, Anita B.
通讯作者：
Roberts, Anita B.
影响因子：
5.6
作者：
Pardali, K;Kowanetz, M;Moustakas, A
通讯作者：
Moustakas, A
DOI：
10.1073/pnas.0409883102
发表时间：
2005-02-15
影响因子：
11.1
作者：
Brake, T;Lambert, PF
通讯作者：
Lambert, PF
影响因子：
168.9
作者：
Moreno, V;Bosch, FX;Franceschi, S
通讯作者：
Franceschi, S
影响因子：
8
作者：
Kang, SH;Bang, YJ;Kim, SJ
通讯作者：
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