Distinct role and functional mode of TR3 and RAR alpha in mediating ATRA-induced signalling pathway in breast and gastric cancer cells
- 生命科学－已发表论文 
All-trans retinoic acid (ATRA) affects cell proliferation, differentiation and apoptosis through its receptors, RARs and RXRs. Besides these, other receptors such as orphan receptor TR3, are also involved in the regulatory process of ATRA. However, how different receptors function in response to ATRA is still largely unknown. In the present study, we found that formation of TR3/RXRalpha heterodimers in the nucleus and their subsequent translocation into the cytoplasm, in association with regulation of apoptosis-related proteins Bcl-2, Bcl-xl and Bax, was critical for apoptosis induction by ATRA in breast cancer cells MCF-7. When such translocation was blocked by Leptomycin B (LMB), ATRA-induced apoptosis was consequently abolished. However, in ATRA-induced gastric cancer cells MGC80-3, RXRalpha heterodimerised with RARalpha but not with TR3, and remained in the nucleus exerting its effect on cell cycle regulation. When transfected with antisense-RARalpha, MGC80-3 cells changed from ATRA-sensitive to ATRA-resistant and most cells were arrested in the S phase, implying the importance of RARalpha in cell cycle regulation. Furthermore, we demonstrated that the effects of ATRA depend on the relative levels of TR3, RARalpha and RXRalpha expression in cancer cells. In ATRA-induced MCF-7 cells, highly expressed TR3 favours the formation of TR3/RXRalpha and promotes the TR3/RXRalpha signalling pathway causing apoptosis; while in ATRA-induced MGC80-3 cells, high expression of RARalpha favours the formation of RARalpha/RXRalpha and promotes the RXRalpha/RARalpha signalling pathway in mediating cell cycle regulation. In conclusion, these results reveal the novel mechanism that cellular expression and location of protein is associated with diverse signalling transduction pathways and the resultant physiological process. (C) 2003 Elsevier Science Ltd. All rights reserved.
CitationInt J Biochem Cell Biol. 2004 Jan;36(1):98-113.
Showing items related by title, author, creator and subject.
Hypoxia-inducible Factor alpha Subunit Stabilization by NEDD8 Conjugation Is Reactive Oxygen Species-dependent Ryu, Ji-Hye; Li, Shan-Hua; Park, Hyoung-Sook; Park, Jong-Wan; Lee, ByungLan; Chun, Yang-Sook; 李顺华 (2011-03-04)Hypoxia-inducible factor alpha proteins (HIF-alpha s) are regulated oxygen dependently and transactivate numerous genes essential for cellular adaptation to hypoxia. NEDD8, a member of the ubiquitin-like family, covalently ...
Nuclear import of aristaless-related homeobox protein via its NLS1 regulates its transcriptional function Ye, Wenduo; Lin, Wenbo; Tartakoff, Alan M.; Ma, Qilin; Tao, Tao; 林文波; 马琪林; 陶涛 (SPRINGER, 2013)Nucleocytoplasmic transport of transcription factors is essential in eukaryotes. We previously reported the presence of two functional NLSs in the homeodomain protein, aristaless-related homeobox (Arx) protein, which is a ...
A double-negative feedback loop between Wnt-beta-catenin signaling and HNF4 alpha regulates epithelial-mesenchymal transition in hepatocellular carcinoma Yang, Meng; Li, Sheng-Nan; Anjum, Khalid M.; Gui, Long-Xin; Zhu, Shan-Shan; Liu, Jun; Chen, Jia-Kun; Liu, Qing-Feng; Ye, Guo-Dong; Wang, Wen-Jie; Wu, Jia-Fa; Cai, Wang-Yu; Sun, Guang-Bin; Liu, Yun-Jia; Liu, Rong-Fu; Zhang, Zhi-Ming; Li, Bo-An; 刘荣福; 张志明; 李博安 (COMPANY OF BIOLOGISTS LTD, 2013-Dec 1)Wnt-beta-catenin signaling participates in the epithelial-mesenchymal transition (EMT) in a variety of cancers; however, its involvement in hepatocellular carcinoma (HCC) and downstream molecular events is largely undefined. ...