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dc.contributor.authorYe, XF
dc.contributor.authorWu, Q
dc.contributor.author吴乔
dc.contributor.authorLiu, S
dc.contributor.authorLin, XF
dc.contributor.authorZhang, B
dc.contributor.authorWu, JF
dc.contributor.authorCai, JH
dc.contributor.authorZhang, MQ
dc.contributor.authorSu, WJ
dc.contributor.author苏文金
dc.date.accessioned2011-10-28T01:43:47Z
dc.date.available2011-10-28T01:43:47Z
dc.date.issued2004
dc.identifier.citationInt J Biochem Cell Biol. 2004 Jan;36(1):98-113.zh_CN
dc.identifier.issn1357-2725
dc.identifier.urihttp://dx.doi.org/doi:10.1016/S1357-2725(03)00143-2
dc.identifier.urihttps://dspace.xmu.edu.cn/handle/2288/11023
dc.description.abstractAll-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.zh_CN
dc.language.isoenzh_CN
dc.publisherPERGAMON-ELSEVIER SCIENCE LTDzh_CN
dc.subjectTR3zh_CN
dc.subjectretinoic acid receptor alpha (RAR alpha)zh_CN
dc.subjectretinoid X receptor alpha (RYR alpha)zh_CN
dc.subjecttranslocationzh_CN
dc.subjectall-trans retinoic acid (ATRA)zh_CN
dc.subjectcancer cellzh_CN
dc.titleDistinct role and functional mode of TR3 and RAR alpha in mediating ATRA-induced signalling pathway in breast and gastric cancer cellszh_CN
dc.typeArticlezh_CN


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