PNAS:颠覆 雌激素在宫颈癌癌中的作用

2015-06-12 生物通 生物通

科学家们一直认为雌激素是宫颈癌生长的主要驱动因子。但一项最新研究表明,雌激素受体在宫颈癌细胞中几乎全部消失。相关论文发表在近期的美国国家科学院院刊PNAS杂志上。宫颈癌是女性中的第二大癌症,在发展中国家尤其常见,因为在那里早期筛查还不普遍。人们发现,几乎所有宫颈癌都是人乳头瘤病毒(HPV)感染引起的。研究人员对SUCCEED项目(Study to Understand Cervical Cance

科学家们一直认为雌激素是宫颈癌生长的主要驱动因子。但一项最新研究表明,雌激素受体在宫颈癌细胞中几乎全部消失。相关论文发表在近期的美国国家科学院院刊PNAS杂志上。

宫颈癌是女性中的第二大癌症,在发展中国家尤其常见,因为在那里早期筛查还不普遍。人们发现,几乎所有宫颈癌都是人乳头瘤病毒(HPV)感染引起的。

研究人员对SUCCEED项目(Study to Understand Cervical Cancer Early Endpoints and Determinants)的128个样本进行了基因表达谱分析,涉及了四个不同的群体:健康人、HPV感染并出现并发症的患者、宫颈癌患者。这四个群体可以体现从病毒感染到癌症发生的整个过程,文章第一作者Wisconsin-Madison大学的Johan den Boon说。

“我们的首要目标是寻找遗传学指标,希望能够预测最有可能发展成癌症的HPV感染,以及最不需要担心的阶段,”den Boon说。

蛋白p16显著增加是HPV相关疾病的标志性事件,这个蛋白与细胞分裂调控有关。研究人员试图通过128个样本的基因表达分析,寻找与p16类似的其他基因。结果他们发现了惊人的现象,“雌激素受体与p16完全相反。健康细胞原本具有雌激素受体,但在细胞癌变的时候,雌激素受体几乎检测不到了。”

此前人们已经研究过响应雌激素的数百个基因,证实雌激素受体和这些基因的水平,是宫颈癌发展过程中的重要指标。因此,Den Boon等人一开始还以为自己的实验出现了错误。他们在进一步研究中观察到,虽然雌激素受体在癌细胞中消失,但它们普遍存在于肿瘤微环境中,往往还有所增加。

这些发现说明,肿瘤和微环境之间发生了关键性的事件,让肿瘤在“看不到”雌激素的情况下生长。“要理解雌激素的真正作用,我们就必须研究肿瘤和微环境如何彼此交流,”den Boon说。

下一步,研究人员将使用微流体技术分析宫颈癌肿瘤的信号传导,解读肿瘤与微环境之间来来回回的生化信号。这将有助于开发小分子药物干扰信号传导,最终抑制肿瘤的生长。

原始出处:

den Boon JA1, Pyeon D2, Wang SS3, Horswill M4, Schiffman M5, Sherman M5, Zuna RE6, Wang Z7, Hewitt SM5, Pearson R8, Schott M9, Chung L7, He Q7, Lambert P10, Walker J6, Newton MA11, Wentzensen N12, Ahlquist P13.Molecular transitions from papillomavirus infection to cervical precancer and cancer: Role of stromal estrogen receptor signaling.Proc Natl Acad Sci U S A. 2015 Jun 8. pii: 201509322. [Epub ahead of print]

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    2015-11-26 drwjr
  2. [GetPortalCommentsPageByObjectIdResponse(id=1855737, encodeId=b8091855e373a, content=<a href='/topic/show?id=f32014428fc' target=_blank style='color:#2F92EE;'>#PNAS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14428, encryptionId=f32014428fc, topicName=PNAS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=08e964, createdName=drwjr, createdTime=Thu Nov 26 12:28:00 CST 2015, time=2015-11-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=29386, encodeId=ee4829386d9, content=看看, beContent=null, objectType=article, channel=null, level=null, likeNumber=124, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ee0d1618732, createdName=huaxipanxing, createdTime=Thu Jun 25 23:42:00 CST 2015, time=2015-06-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=28188, encodeId=8e6628188ed, content=?, beContent=null, objectType=article, channel=null, level=null, likeNumber=112, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20150830/IMG55E294026A9942981.jpg, createdBy=fa351627501, createdName=惜言, createdTime=Fri Jun 19 15:35:00 CST 2015, time=2015-06-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1407954, encodeId=0086140e954b3, content=<a href='/topic/show?id=92194628826' target=_blank style='color:#2F92EE;'>#宫颈#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=46288, encryptionId=92194628826, topicName=宫颈)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=55683, createdName=仁医06, createdTime=Sun Jun 14 07:28:00 CST 2015, time=2015-06-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=27419, encodeId=332e2e41998, content=真是大师级的研究, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=db141627504, createdName=chenguoyan, createdTime=Sat Jun 13 01:18:00 CST 2015, time=2015-06-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=27420, encodeId=403d2e420e3, content=?, beContent=null, objectType=article, channel=null, level=null, likeNumber=112, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=db141627504, createdName=chenguoyan, createdTime=Sat Jun 13 01:18:00 CST 2015, time=2015-06-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=27421, encodeId=a5c02e421bf, content=?, beContent=null, objectType=article, channel=null, level=null, likeNumber=107, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=db141627504, createdName=chenguoyan, createdTime=Sat Jun 13 01:18:00 CST 2015, time=2015-06-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=27381, encodeId=919e2e381e6, content=这么说雌激素有可能不影响宫颈癌了!, beContent=null, objectType=article, channel=null, level=null, likeNumber=92, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=02ae1614916, createdName=liuxu6026, createdTime=Fri Jun 12 22:21:00 CST 2015, time=2015-06-12, status=1, ipAttribution=)]
    2015-06-25 huaxipanxing

    看看

    0

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    2015-06-19 惜言

    0

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    2015-06-14 仁医06
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    2015-06-13 chenguoyan

    真是大师级的研究

    0

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    2015-06-13 chenguoyan

    ?

    0

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    2015-06-13 chenguoyan

    ?

    0

  8. [GetPortalCommentsPageByObjectIdResponse(id=1855737, encodeId=b8091855e373a, content=<a href='/topic/show?id=f32014428fc' target=_blank style='color:#2F92EE;'>#PNAS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14428, encryptionId=f32014428fc, topicName=PNAS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=08e964, createdName=drwjr, createdTime=Thu Nov 26 12:28:00 CST 2015, time=2015-11-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=29386, encodeId=ee4829386d9, content=看看, beContent=null, objectType=article, channel=null, level=null, likeNumber=124, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ee0d1618732, createdName=huaxipanxing, createdTime=Thu Jun 25 23:42:00 CST 2015, time=2015-06-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=28188, encodeId=8e6628188ed, content=?, beContent=null, objectType=article, channel=null, level=null, likeNumber=112, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20150830/IMG55E294026A9942981.jpg, createdBy=fa351627501, createdName=惜言, createdTime=Fri Jun 19 15:35:00 CST 2015, time=2015-06-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1407954, encodeId=0086140e954b3, content=<a href='/topic/show?id=92194628826' target=_blank style='color:#2F92EE;'>#宫颈#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=46288, encryptionId=92194628826, topicName=宫颈)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=55683, createdName=仁医06, createdTime=Sun Jun 14 07:28:00 CST 2015, time=2015-06-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=27419, encodeId=332e2e41998, content=真是大师级的研究, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=db141627504, createdName=chenguoyan, createdTime=Sat Jun 13 01:18:00 CST 2015, time=2015-06-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=27420, encodeId=403d2e420e3, content=?, beContent=null, objectType=article, channel=null, level=null, likeNumber=112, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=db141627504, createdName=chenguoyan, createdTime=Sat Jun 13 01:18:00 CST 2015, time=2015-06-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=27421, encodeId=a5c02e421bf, content=?, beContent=null, objectType=article, channel=null, level=null, likeNumber=107, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=db141627504, createdName=chenguoyan, createdTime=Sat Jun 13 01:18:00 CST 2015, time=2015-06-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=27381, encodeId=919e2e381e6, content=这么说雌激素有可能不影响宫颈癌了!, beContent=null, objectType=article, channel=null, level=null, likeNumber=92, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=02ae1614916, createdName=liuxu6026, createdTime=Fri Jun 12 22:21:00 CST 2015, time=2015-06-12, status=1, ipAttribution=)]
    2015-06-12 liuxu6026

    这么说雌激素有可能不影响宫颈癌了!

    0

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