HDAC Inhibition Decreases the Expression of EGFR in Colorectal Cancer Cells

被引：93

作者：

Chou, Chia-Wei ^{[1
]}

Wu, Ming-Shiang ^{[2
,3
]}

Huang, Wei-Chien ^{[4
,5
]}

Chen, Ching-Chow ^{[1
]}

机构：

[1] Natl Taiwan Univ, Coll Med, Dept Pharmacol, Taipei 10764, Taiwan

[2] Natl Taiwan Univ, Coll Med, Dept Internal Med & Primary Care Med, Div Gastroenterol, Taipei 10764, Taiwan

[3] Natl Taiwan Univ Hosp, Taipei, Taiwan

[4] China Med Univ, Grad Inst Canc Biol, Taichung, Taiwan

[5] China Med Univ Hosp, Ctr Mol Med, Taichung, Taiwan

来源：

PLOS ONE | 2011年 / 6卷 / 03期

关键词：

GROWTH-FACTOR RECEPTOR; HISTONE DEACETYLASE INHIBITOR; COLON-CANCER; GENE-EXPRESSION; TYROSINE KINASE; LUNG-CANCER; TRANSCRIPTION; SURVIVAL; APOPTOSIS; CETUXIMAB;

D O I：

10.1371/journal.pone.0018087

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Epidermal growth factor receptor (EGFR), a receptor tyrosine kinase which promotes cell proliferation and survival, is abnormally overexpressed in numerous tumors of epithelial origin, including colorectal cancer (CRC). EGFR monoclonal antibodies have been shown to increase the median survival and are approved for the treatment of colorectal cancer. Histone deacetylases (HDACs), frequently overexpressed in colorectal cancer and several malignancies, are another attractive targets for cancer therapy. Several inhibitors of HDACs (HDACi) are developed and exhibit powerful antitumor abilities. In this study, human colorectal cancer cells treated with HDACi exhibited reduced EGFR expression, thereby disturbed EGF-induced ERK and Akt phosphorylation. HDACi also decreased the expression of SGLT1, an active glucose transporter found to be stabilized by EGFR, and suppressed the glucose uptake of cancer cells. HDACi suppressed the transcription of EGFR and class I HDACs were proved to be involved in this event. Chromatin immunoprecipitation analysis showed that HDACi caused the dissociation of SP1, HDAC3 and CBP from EGFR promoter. Our data suggested that HDACi could serve as a single agent to block both EGFR and HDAC, and may bring more benefits to the development of CRC therapy.

引用

页数：12