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Distinct role and functional mode of TR3 and RAR alpha in mediating ATRA-induced signalling pathway in breast and gastric cancer cells
Ye, XF ; Wu, Q ; Wu Q(吴乔) ; Liu, S ; Lin, XF ; Zhang, B ; Wu, JF ; Cai, JH ; Zhang, MQ ; Su, WJ ; Su WJ(苏文金)
2004
关键词TR3 retinoic acid receptor alpha (RAR alpha) retinoid X receptor alpha (RYR alpha) translocation all-trans retinoic acid (ATRA) cancer cell
英文摘要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.
语种英语
出版者PERGAMON-ELSEVIER SCIENCE LTD
内容类型期刊论文
源URL[http://dx.doi.org/doi:10.1016/S1357-2725(03)00143-2]  
专题生命科学-已发表论文
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GB/T 7714
Ye, XF,Wu, Q,Wu Q,et al. Distinct role and functional mode of TR3 and RAR alpha in mediating ATRA-induced signalling pathway in breast and gastric cancer cells[J],2004.
APA Ye, XF.,Wu, Q.,吴乔.,Liu, S.,Lin, XF.,...&苏文金.(2004).Distinct role and functional mode of TR3 and RAR alpha in mediating ATRA-induced signalling pathway in breast and gastric cancer cells..
MLA Ye, XF,et al."Distinct role and functional mode of TR3 and RAR alpha in mediating ATRA-induced signalling pathway in breast and gastric cancer cells".(2004).
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