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Biochem Biophys Res Commun. 2018 Apr 6;498(3):566-572. doi: 10.1016/j.bbrc.2018.03.020. Epub 2018 Mar 13.

Downregulation of TXNIP leads to high proliferative activity and estrogen-dependent cell growth in breast cancer.

Author information

1
Department of Veterinary Pathology, Department of Veterinary Pathology, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea.
2
Laboratory of Histopathology, Department of Clinical Laboratory Science, Semyung University, Jecheon 27136, Republic of Korea.
3
Department of Veterinary Pathology, College of Veterinary Medicine, Chungnam National University, Daejeon, Republic of Korea.
4
Department of Veterinary Pathology, Department of Veterinary Pathology, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea. Electronic address: daeyong@snu.ac.kr.

Abstract

TXNIP is a potent tumor suppressor with reduced expression in various types of human cancer. The prognostic and predictive power of TXNIP has been recognized in human breast cancer. The aim of this study is to investigate the clinical relevance and functional roles of TXNIP downregulation in breast cancer. We examined TXNIP expression at the protein level in tissue microarray (TMA)-based human breast cancers and its correlation with clinical parameters and molecular markers on immunohistochemistry (IHC). Compared with normal tissues, TXNIP expression was significantly decreased in human breast cancer tissues and animal mammary tumors, along with tumor progression. TXNIP was restored immediately after histone deacetylase inhibitor treatment in breast cancer cells, implying transcriptional regulation of TXNIP by histone modification. Decreased TXNIP protein levels were more common in tumors showing high proliferative activity, such as high Ki-67 labeling indexes and low p27 expression. TXNIP knockdown led to increased in vitro and in vivo breast cancer cell growth accompanied by p27 reduction and GLUT1 induction. Interestingly, estrogen receptor (ER)-positive breast cancer samples showed higher TXNIP expression compared to ER-negative samples. TXNIP expression decreased when ER signaling was activated by estradiol, while its expression increased under ER blockage by anti-estrogen fulvestrant. In addition, TXNIP knockdown in breast cancer cells caused significant reduction in the cell-growth inhibitory effect of anti-estrogen fulvestrant. In conclusion, our data demonstrated that TXNIP functions to suppress high proliferative activity and estrogen-dependent cell growth in breast cancer.

KEYWORDS:

Estrogen receptor; Fulvestrant; GLUT1; VDUP1; p27

PMID:
29524408
DOI:
10.1016/j.bbrc.2018.03.020
[Indexed for MEDLINE]

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