Overexpression of transforming growth factor β‐type II receptor reduces tumorigenicity and metastastic potential of K‐ras‐transformed thyroid cells
Overexpression of transforming growth factor β‐type II receptor reduces tumorigenicity and metastastic potential of K‐ras‐transformed thyroid cells
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转化生长因子β-II型受体的过度表达可降低K-ras转化甲状腺细胞的致瘤性和转移潜力
DOI：
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
G. Colletta
中科院分区：
文献类型：
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作者：
A. Turco;A. Coppa;S. Aloe;G. Baccheschi;S. Morrone;G. Zupi;G. Colletta
转化生长因子β（transforming growth factor beta，TβRII）Ⅱ型受体的表达是该因子抑制甲状腺上皮细胞生长所必需的。在大鼠甲状腺转化细胞中，对转化生长因子β（TGFβ）的抗性与Tβ R Ⅱ mRNA和蛋白表达的降低有关。在人甲状腺分化癌和未分化癌中也发现TβRII表达减少。为了研究TβRII在调节k-ras-转化甲状腺细胞致瘤潜力中的作用，我们用携带人TβRII基因的表达载体转染这些细胞，该基因由诱导型启动子调控。过表达TβRII的分离克隆显示，与对照k-ras转化细胞相比，锚定依赖性和非依赖性细胞生长减少。当移植到无胸腺裸鼠中时，转染的克隆相对于高度恶性的亲本细胞呈现致瘤性降低。此外，研究的克隆的致瘤能力降低伴随着自发性和肺人工转移的统计学显著减少。综上所述，我们的数据表明，TβRII作为一个强大的肿瘤抑制基因时，在恶性甲状腺细胞过表达。Int. J. Cancer 80：85-91，1999.© 1999 Wiley利斯公司
Expression of type II receptor of transforming growth factor beta (TβRII) is necessary for this factor to inhibit the growth of thyroid epithelial cells. In rat thyroid transformed cells, the resistance to transforming growth factor beta (TGFβ) is associated with a decreased expression of TβRII mRNA and protein. Reduced TβRII expression has also been found in human thyroid differentiated and undifferentiated carcinomas. To investigate the role of TβRII in modulating the tumorigenic potential of k‐ras‐transformed thyroid cells, we transfected these cells with an expression vector carrying the human TβRII gene, regulated by an inducible promoter. Isolated clones, overexpressing TβRII, showed a reduction in the anchorage‐dependent and ‐independent cell growth, compared with control k‐ras‐transformed cells. When transplanted in athymic nude mice, the transfected clones presented a decrease in tumorigenicity with respect to the highly malignant parental cells. Moreover, the diminished tumorigenic ability of the clones studied was accompanied by a statistically significant reduction in spontaneous and lung artificial metastases. Taken together, our data demonstrate that TβRII acts as a potent tumor suppressor gene when overexpressed in malignant thyroid cells. Int. J. Cancer 80:85–91, 1999. © 1999 Wiley‐Liss, Inc.
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DOI：
10.1210/jcem.75.6.1464638
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DOI：
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发表时间：
1997
期刊：
Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research
影响因子：
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作者：
Okamoto,M;Oyasu,R
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Oyasu,R