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Overexpression of modified human TR?1 suppresses the growth of hepatocarcinoma SK-hep1 cells in vitro and in xenograft models.

ABSTRACT: Association studies suggest that TR?1 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 TR?1 (m-TR?1) via the introduction of a 108-bp exon sequence into the corresponding position of the wild-type human TR?1 (TR?1) DBD. Studies confirmed that m-TR?1 was functional and could inhibit the proliferation of breast cancer MDA-MB-468 cells in vitro. To understand the role of m-TR?1 in liver tumor development, we adopted a gain-of-function approach by stably expressing TR? (m-TR?1 and TR?1) genes in a human hepatocarcinoma cell line, SK-hep1 (without endogenous TR?), and then evaluated the effects of the expressed TR? 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 TR? 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. TR? expression in SK-hep1 led to less tumor growth in xenograft models. Additionally, the anti-tumor effect of m-TR?1 was stronger than that of TR?1. These data indicate that m-TR?1 can act as a tumor suppressor in hepatocarcinoma and its role was significantly better than that of TR?1.

SUBMITTER: Peng X

PROVIDER: S-EPMC6223806 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Overexpression of modified human TRβ1 suppresses the growth of hepatocarcinoma SK-hep1 cells in vitro and in xenograft models.

Peng Xiaoxiang X Zhou Yuntao Y Sun Yanli Y Song Wei W Meng Xiangying X Zhao Chunling C Zhao Ronglan R

Molecular and cellular biochemistry 20180420 1-2

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 vi ...[more]

PMID: 29679278

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Dataset Information

Overexpression of modified human TR?1 suppresses the growth of hepatocarcinoma SK-hep1 cells in vitro and in xenograft models.

Publications

Overexpression of modified human TRβ1 suppresses the growth of hepatocarcinoma SK-hep1 cells in vitro and in xenograft models.

Similar Datasets

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