Cancer Res:重磅!首次确认HER2驱动型乳腺癌与该雌激素受体结合蛋白有关!

2018-01-10 Ruthy,Yui 转化医学网

MED1是一种存在于乳腺癌细胞中,可异常高水平表达的蛋白质,当其被消除时能够阻止乳腺癌细胞的生长,而乳腺癌中由人表皮生长因子受体2(HER2)编码的蛋白质,可促进癌细胞的生长。

MED1是一种存在于乳腺癌细胞中,可异常高水平表达的蛋白质,当其被消除时能够阻止乳腺癌细胞的生长,而乳腺癌中由人表皮生长因子受体2(HER2)编码的蛋白质,可促进癌细胞的生长。

加州大学(UC)医学院的研究人员发现,雌激素受体结合蛋白MED1是HER2驱动型乳腺癌的重要介质,并将其确定为潜在的治疗靶点。该研究结果以《HER2-driven Breast Tumorigenesis Relies upon Interactions of the Estrogen Receptor with Coactivator MED1》为题发表在1月8日的《Cancer Research》在线版上,作者指出,这项研究将为侵袭性和抗性乳腺癌带来更为有效的治疗方法。

UC医学院癌症生物学系副教授Xiaoting Zhang博士说:“目前,乳腺癌仍然是最常见的癌症之一,也是美国女性死亡的主要原因之一。过往研究以雌激素受体,孕激素受体和HER2的基因表达为依据将乳腺癌分为几种亚型。MED1是一种在雌激素受体依赖型乳腺发育和乳腺癌发展过程中发挥作用的雌激素受体共激活因子。MED1基因所在位置与HER2非常接近,常与HER2基因融合,MED1蛋白水平与HER2阳性乳腺癌高度相关。此外,我们还发现HER2可激活MED1,因此MED1可作为治疗耐药性HER2和雌激素受体双阳性乳腺癌中的关键交界点,但MED1在HER2驱动型乳腺癌发生及发展中的作用和其分子功能仍需做进一步研究。”

据该论文的作者介绍,研究人员用HER2和MED1双突变的动物模型来评估MED1蛋白在乳腺癌进展和转移中的作用。雌激素受体可特异性地结合MED1蛋白的LxxLL基序,研究人员发现如果LxxLL基序发生了突变,就会破坏其与雌激素受体的相互作用,从而显着延迟肿瘤的生长、扩散和癌症干细胞的形成。这是第一个证明MED1及其LxxLL基序在乳腺癌的形成、转移和癌症干细胞的形成中起关键作用的证据,也是首次在HER2扩增的癌症中进一步研究MED1的作用机制。

研究结果显示,MED1可直接作用于下游IGF-1途径,从而调节雌激素的信号传导。该途径在乳腺癌的发生发展中起关键作用。更重要的是,他们还发现MED1和IGF-1蛋白水平之间具有强相关性,这进一步说明了MED1及其LXXLL基序成为乳腺癌治疗靶点的潜力。

Xiaoting Zhang博士说,“结合我们之前有关MED1组织特异性作用的结论和此次的成果,现在可以进一步研究如何将MED1作为特异性治疗靶点。目前,我们的团队正在使用RNA纳米技术来选择可与特定靶分子结合的RNA分子,从而实现特异性靶向MED1的LxxLL基序,以破坏MED1 /雌激素受体的相互作用。”

原始出处:

版权声明:
本网站所有内容来源注明为“梅斯医学”或“MedSci原创”的文字、图片和音视频资料,版权均属于梅斯医学所有。非经授权,任何媒体、网站或个人不得转载,授权转载时须注明来源为“梅斯医学”。其它来源的文章系转载文章,或“梅斯号”自媒体发布的文章,仅系出于传递更多信息之目的,本站仅负责审核内容合规,其内容不代表本站立场,本站不负责内容的准确性和版权。如果存在侵权、或不希望被转载的媒体或个人可与我们联系,我们将立即进行删除处理。
在此留言
评论区 (4)
#插入话题
  1. [GetPortalCommentsPageByObjectIdResponse(id=1503484, encodeId=62c81503484c2, content=<a href='/topic/show?id=59d798e61f0' target=_blank style='color:#2F92EE;'>#雌激素受体#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=98761, encryptionId=59d798e61f0, topicName=雌激素受体)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ae6c9649886, createdName=surilei, createdTime=Fri Jan 12 13:04:00 CST 2018, time=2018-01-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1549263, encodeId=773315492634d, content=<a href='/topic/show?id=f7879600061' target=_blank style='color:#2F92EE;'>#重磅#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=22, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=96000, encryptionId=f7879600061, topicName=重磅)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=3acc14121561, createdName=xxxx1054, createdTime=Fri Jan 12 13:04:00 CST 2018, time=2018-01-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=277350, encodeId=31772e7350a2, content=学习学习学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=60, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzR8ylhYfiaoAUx2BsaYHVia1IKhG3Cg8CT84rBrn6iaVRkyAibJxBcLEXabOQ5p19vWgDe34ib5ErxNgx/0, createdBy=8a701629084, createdName=jihuaijun1112, createdTime=Thu Jan 11 01:55:04 CST 2018, time=2018-01-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=277311, encodeId=5fe62e73117f, content=.谢谢分享学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/Q3auHgzwzM7GibvIBibibnnnvpajk2stlDF5oichYahI6Bia8uxeTBFoPbdoHWebyXf9eal9FNgUF2lNcrwoZicM3BvQ/0, createdBy=a3742066385, createdName=戒馋,懒,贪, createdTime=Wed Jan 10 22:11:21 CST 2018, time=2018-01-10, status=1, ipAttribution=)]
  2. [GetPortalCommentsPageByObjectIdResponse(id=1503484, encodeId=62c81503484c2, content=<a href='/topic/show?id=59d798e61f0' target=_blank style='color:#2F92EE;'>#雌激素受体#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=98761, encryptionId=59d798e61f0, topicName=雌激素受体)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ae6c9649886, createdName=surilei, createdTime=Fri Jan 12 13:04:00 CST 2018, time=2018-01-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1549263, encodeId=773315492634d, content=<a href='/topic/show?id=f7879600061' target=_blank style='color:#2F92EE;'>#重磅#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=22, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=96000, encryptionId=f7879600061, topicName=重磅)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=3acc14121561, createdName=xxxx1054, createdTime=Fri Jan 12 13:04:00 CST 2018, time=2018-01-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=277350, encodeId=31772e7350a2, content=学习学习学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=60, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzR8ylhYfiaoAUx2BsaYHVia1IKhG3Cg8CT84rBrn6iaVRkyAibJxBcLEXabOQ5p19vWgDe34ib5ErxNgx/0, createdBy=8a701629084, createdName=jihuaijun1112, createdTime=Thu Jan 11 01:55:04 CST 2018, time=2018-01-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=277311, encodeId=5fe62e73117f, content=.谢谢分享学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/Q3auHgzwzM7GibvIBibibnnnvpajk2stlDF5oichYahI6Bia8uxeTBFoPbdoHWebyXf9eal9FNgUF2lNcrwoZicM3BvQ/0, createdBy=a3742066385, createdName=戒馋,懒,贪, createdTime=Wed Jan 10 22:11:21 CST 2018, time=2018-01-10, status=1, ipAttribution=)]
    2018-01-12 xxxx1054
  3. [GetPortalCommentsPageByObjectIdResponse(id=1503484, encodeId=62c81503484c2, content=<a href='/topic/show?id=59d798e61f0' target=_blank style='color:#2F92EE;'>#雌激素受体#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=98761, encryptionId=59d798e61f0, topicName=雌激素受体)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ae6c9649886, createdName=surilei, createdTime=Fri Jan 12 13:04:00 CST 2018, time=2018-01-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1549263, encodeId=773315492634d, content=<a href='/topic/show?id=f7879600061' target=_blank style='color:#2F92EE;'>#重磅#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=22, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=96000, encryptionId=f7879600061, topicName=重磅)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=3acc14121561, createdName=xxxx1054, createdTime=Fri Jan 12 13:04:00 CST 2018, time=2018-01-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=277350, encodeId=31772e7350a2, content=学习学习学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=60, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzR8ylhYfiaoAUx2BsaYHVia1IKhG3Cg8CT84rBrn6iaVRkyAibJxBcLEXabOQ5p19vWgDe34ib5ErxNgx/0, createdBy=8a701629084, createdName=jihuaijun1112, createdTime=Thu Jan 11 01:55:04 CST 2018, time=2018-01-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=277311, encodeId=5fe62e73117f, content=.谢谢分享学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/Q3auHgzwzM7GibvIBibibnnnvpajk2stlDF5oichYahI6Bia8uxeTBFoPbdoHWebyXf9eal9FNgUF2lNcrwoZicM3BvQ/0, createdBy=a3742066385, createdName=戒馋,懒,贪, createdTime=Wed Jan 10 22:11:21 CST 2018, time=2018-01-10, status=1, ipAttribution=)]
    2018-01-11 jihuaijun1112

    学习学习学习

    0

  4. [GetPortalCommentsPageByObjectIdResponse(id=1503484, encodeId=62c81503484c2, content=<a href='/topic/show?id=59d798e61f0' target=_blank style='color:#2F92EE;'>#雌激素受体#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=98761, encryptionId=59d798e61f0, topicName=雌激素受体)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ae6c9649886, createdName=surilei, createdTime=Fri Jan 12 13:04:00 CST 2018, time=2018-01-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1549263, encodeId=773315492634d, content=<a href='/topic/show?id=f7879600061' target=_blank style='color:#2F92EE;'>#重磅#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=22, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=96000, encryptionId=f7879600061, topicName=重磅)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=3acc14121561, createdName=xxxx1054, createdTime=Fri Jan 12 13:04:00 CST 2018, time=2018-01-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=277350, encodeId=31772e7350a2, content=学习学习学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=60, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzR8ylhYfiaoAUx2BsaYHVia1IKhG3Cg8CT84rBrn6iaVRkyAibJxBcLEXabOQ5p19vWgDe34ib5ErxNgx/0, createdBy=8a701629084, createdName=jihuaijun1112, createdTime=Thu Jan 11 01:55:04 CST 2018, time=2018-01-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=277311, encodeId=5fe62e73117f, content=.谢谢分享学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/Q3auHgzwzM7GibvIBibibnnnvpajk2stlDF5oichYahI6Bia8uxeTBFoPbdoHWebyXf9eal9FNgUF2lNcrwoZicM3BvQ/0, createdBy=a3742066385, createdName=戒馋,懒,贪, createdTime=Wed Jan 10 22:11:21 CST 2018, time=2018-01-10, status=1, ipAttribution=)]
    2018-01-10 戒馋,懒,贪

    .谢谢分享学习了

    0