Decreased stability of transforming growth factor beta type II receptor mRNA in RER+ human colon carcinoma cells.
Decreased stability of transforming growth factor beta type II receptor mRNA in RER+ human colon carcinoma cells.
复制标题
RER 人结肠癌细胞中转化生长因子 β II 型受体 mRNA 的稳定性降低。
DOI：
10.1021/bi9717892
复制
发表时间：
1997
期刊：
影响因子：
2.9
通讯作者：
Banerji,SS
中科院分区：
文献类型：
--
作者：
Jiang,W;Tillekeratne,MP;Brattain,MG;Banerji,SS
Transforming growth factor β (TGF-β) is a potent inhibitor of cell growth and tumor progression. Previous work has shown that loss of functional TGF-β type II receptor (RII) due to a frameshift mutation in the 5‘ half of the RII gene leads to TGF-β resistance in a highly progressed, RER+human colon carcinoma cell line designated HCT116. Expression of this mutated RII gene was highly repressed in RER+cell lines such as HCT116 and RKO, as analyzed by RNase protection assays. Nuclear run-on and RII promoter−reporter (CAT) assays showed that the transcriptional levels of the RII gene in these RER+cells were not reduced, compared to RII-expressing cells. However, the half-lives of the RII mRNA, as analyzed by RNase protection assays following actinomycin D treatment, were significantly decreased. This suggested that the decreased expression of the RII gene mutant was due to decreased mRNA stability. Furthermore, RII mRNA from HCT116 transfected with wild-type RII had a longer half-life than the endogenous mutated RII mRNA. A dominant negative RII mutant, which encodes a similarly truncated RII protein as HCT116 but lacks the extensive 3‘ untranslated region of RII mRNA, gave the same half-life as endogenous wild-type RII mRNA. We conclude that the frameshift mutation which results in a premature stop codon in the 5‘ half of the mRNA transcript accounts for the reduced RII mRNA levels in RER+cells.
