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

Park, Jun Won ; Lee, Su Hyung ; Woo, Gye-Hyung ; Kwon, Hyo-Jung ; Kim, Dae-Yong

Biochemical and biophysical research communications, 2018-04, Vol.498 (3), p.566-572 [Periódico revisado por pares]

United States: Elsevier Inc

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Título:
Downregulation of TXNIP leads to high proliferative activity and estrogen-dependent cell growth in breast cancer
Autor: Park, Jun Won ; Lee, Su Hyung ; Woo, Gye-Hyung ; Kwon, Hyo-Jung ; Kim, Dae-Yong
Assuntos: Animals ; Breast - metabolism ; Breast - pathology ; Breast Neoplasms - genetics ; Breast Neoplasms - metabolism ; Breast Neoplasms - pathology ; Carrier Proteins - analysis ; Carrier Proteins - genetics ; Carrier Proteins - metabolism ; Cell Line, Tumor ; Cell Proliferation ; Dog Diseases - genetics ; Dog Diseases - metabolism ; Dog Diseases - pathology ; Dogs ; Down-Regulation ; Estrogen receptor ; Estrogens - metabolism ; Female ; Fulvestrant ; Gene Expression Regulation, Neoplastic ; GLUT1 ; Humans ; Mammary Neoplasms, Animal - genetics ; Mammary Neoplasms, Animal - metabolism ; Mammary Neoplasms, Animal - pathology ; p27 ; VDUP1
É parte de: Biochemical and biophysical research communications, 2018-04, Vol.498 (3), p.566-572
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SourceType-Scholarly Journals-1
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Descrição: 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. •TXNIP is downregulated in human breast cancers and animal mammary tumor models.•TXNIP downregulation leads to breast cancer cell growth.•TXNIP downregulation reduces sensitivity to anti-estrogen fulvestrant.
Editor: United States: Elsevier Inc
Idioma: Inglês

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

Park, Jun Won ; Lee, Su Hyung ; Woo, Gye-Hyung ; Kwon, Hyo-Jung ; Kim, Dae-Yong

United States: Elsevier Inc

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