Expression of transforming growth factor β type II receptor leads to reduced malignancy in human breast cancer MCF-7 cells
Expression of transforming growth factor β type II receptor leads to reduced malignancy in human breast cancer MCF-7 cells
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DOI：
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发表时间：
1994-10
影响因子：
4.8
通讯作者：
Lunquan Sun;Gengfei Wu;J. Willson;E. Zborowska;Junhua Yang;I. Rajkarunanayake;Jing Wang;L. Gentry;Xiao-Fan Wang;M. Brattain
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作者：
Lunquan Sun;Gengfei Wu;J. Willson;E. Zborowska;Junhua Yang;I. Rajkarunanayake;Jing Wang;L. Gentry;Xiao-Fan Wang;M. Brattain
摘要 研究了转化生长因子 (TGF) β II 型受体在逆转人乳腺癌 MCF-7 细胞恶性表型中的作用。 MCF-7 细胞对 TGF beta 1 不敏感，并通过与 125I-TGF beta 1 交联表达不可检测水平的细胞表面 TGF beta I 型受体 (RI) 和 II 型受体 (RII)。RII 表达载体的稳定转染产生了 3 个具有不同水平外源 RII mRNA 和蛋白质水平的转染子。 RII 的表达还增加了所有 3 个克隆中 TGF beta 1 与 RI 的结合。 RII阳性克隆的增殖被外源TGFβ1以剂量依赖性方式抑制，而对照克隆仍然对TGFβ不敏感。 RII转染子在单层培养物中生长停滞，饱和密度为Neo对照的41-66%。它们还显示软琼脂糖中的克隆形成性降低。低RII水平的转染子在切除卵巢、补充雌激素的裸鼠中的致瘤性被延迟。表达高水平 RII 的转染子表现出致瘤性大大降低以及肿瘤形成的延迟更长。肿瘤生长与转染子中外源RII表达的丧失相关。结果表明，当 TGF β 信号转导系统完好无损时，TGF β 受体系统的重建可以导致缺乏 RII 的细胞恶性肿瘤的逆转。
Abstract The role of transforming growth factor (TGF) beta type II receptor in reversing the malignant phenotype of human breast cancer MCF-7 cells was examined. MCF-7 cells were insensitive to TGF beta 1 and expressed undetectable levels of cell surface TGF beta type I receptor (RI) and type II receptor (RII) by cross-linking with 125I-TGF beta 1. Stable transfection of a RII expression vector yielded 3 transfectants with varying levels of exogenous RII mRNA and protein levels. Expression of RII also increased TGF beta 1 binding to RI in all 3 clones. Proliferation of RII-positive clones was inhibited by exogenous TGF beta 1 in a dose-dependent manner, whereas the control clones remained TGF beta-insensitive. The RII transfectants were growth arrested in monolayer culture at saturation densities which were 41-66% of that of the Neo controls. They also showed reduced clonogenicity in soft-agarose. Tumorigenicity in ovariectomized, estrogen-supplemented nude mice was delayed in transfectants with low RII levels. Transfectants expressing high levels of RII showed a large reduction in tumorigenicity as well as a longer delay in tumor formation. Tumor growth was associated with loss of exogenous RII expression in transfectants. The results indicate that when systems for TGF beta signal transduction are intact, reconstitution of the TGF beta receptor system can lead to reversion of malignancy in cells lacking RII.