연구논문

세부과제번호 2016M3A9D5A01952416 단계 2단계 2차년도
세부과제명 유전자변형마우스 병리표현형 분석서비스시스템 구축 및 운용 공동 유/무 N
SCI여부 Y 게재년월 -
논문제목 Downregulation of TXNIP leads to high proliferative activity and estrogen-dependent cell growth in breast cancer.
총저자명 Jun Won Park, Su Hyung Lee, Gye-Hyung Woo, Hyo-Jung Kwon, Dae-Yong Kim
학술지명 Biochem. Biophys. Res. Commun. 게재권(호) 498(3)
저널구분 - 페이지수 566-572
참여연구원 - 연구책임자 남기택
과제기여도 30 PMID 29524408
사사기관수 - IF (년도) 2.559
제1저자 Jun Won Park 교신저자 Dae-Yong Kim
공동저자 Su Hyung Lee, Gye-Hyung Woo, Hyo-Jung Kwon
초록
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.
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