Overexpressing modified human TR?1 suppresses the proliferation of breast cancer MDA-MB-468 cells.

ABSTRACT: A number of studies have indicated that thyroid hormone receptor ?1 (TR?1) functions as a tumor suppressor. TRs mediate transcriptional responses through a highly conserved DNA-binding domain (DBD). A novel rat TR? isoform (rTR??) was previously identified, in which a novel exon, N (108 bp), is located between exons 3 and 4 within the DBD; this exon represents the only difference between rTR?? and rTR?1. In vitro, rTR?? exhibits a stronger tumor-suppressive capacity than rTR?1, and further analysis revealed a high level of conservation between the rat and human DBD sequences. In the present study, an artificially modified human TR?1 (m-hTR?1) was constructed via the introduction of the 108-bp sequence into the corresponding position of the wild-type human TR?1 (wt-hTR?1) DBD. An electrophoretic mobility shift assay and transfection experiments confirmed that m-hTR?1 is functional. Overexpression of m-hTR?1 inhibits the proliferation of MDA-MB-468 cells in the presence of triiodothyronine by promoting apoptosis, which may be associated with the upregulation of Caspase-3 and Bak gene expression and the activation of the Caspase-3 protein. In addition, the pro-apoptotic effect of m-hTR?1 was stronger, compared with wt-hTR?1. These results indicated that m-hTR?1 may act as a tumor suppressor in MDA-MB-468 cells. These data provided a novel insight into gene therapy for breast cancer.

SUBMITTER: Peng X 

PROVIDER: S-EPMC6019938 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature