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- Title
Overexpression of modified human TRβ1 suppresses the growth of hepatocarcinoma SK-hep1 cells in vitro and in xenograft models.
- Authors
Peng, Xiaoxiang; Zhou, Yuntao; Sun, Yanli; Song, Wei; Meng, Xiangying; Zhao, Chunling; Zhao, Ronglan
- Abstract
Association studies suggest that TRβ1 functions as a tumor suppressor. Thyroid hormone receptors (TRs) mediate transcriptional responses through a highly conserved DNA-binding domain (DBD). We previously constructed an artificially modified human TRβ1 (m-TRβ1) via the introduction of a 108-bp exon sequence into the corresponding position of the wild-type human TRβ1 (TRβ1) DBD. Studies confirmed that m-TRβ1 was functional and could inhibit the proliferation of breast cancer MDA-MB-468 cells in vitro. To understand the role of m-TRβ1 in liver tumor development, we adopted a gain-of-function approach by stably expressing TRβ (m-TRβ1 and TRβ1) genes in a human hepatocarcinoma cell line, SK-hep1 (without endogenous TRβ), and then evaluated the effects of the expressed TRβ on cancer cell proliferation, migration, and tumor growth in cell-based studies and xenograft models. In the presence of 3,5,3-L-triiodothyronine (T3), the expression of TRβ in SK-hep1 cells inhibited cancer cell proliferation and impeded tumor cell migration through the up-regulation of 4-1BB, Caspase-3, and Bak gene expression; down-regulation of Bcl-2 gene expression; and activation of the Caspase-3 protein. TRβ expression in SK-hep1 led to less tumor growth in xenograft models. Additionally, the anti-tumor effect of m-TRβ1 was stronger than that of TRβ1. These data indicate that m-TRβ1 can act as a tumor suppressor in hepatocarcinoma and its role was significantly better than that of TRβ1.
- Subjects
DNA-binding proteins; THYROID hormone receptors; TRIIODOTHYRONINE; CANCER cell proliferation; CELL lines; XENOGRAFTS
- Publication
Molecular & Cellular Biochemistry, 2018, Vol 449, Issue 1/2, p207
- ISSN
0300-8177
- Publication type
Article
- DOI
10.1007/s11010-018-3357-1