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首页> 外文期刊>Cancer biology & therapy >Elevated Src kinase activity attenuates Tamoxifen response in vitro and is associated with poor prognosis clinically.
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Elevated Src kinase activity attenuates Tamoxifen response in vitro and is associated with poor prognosis clinically.

机译：Src激酶活性升高会减弱他莫昔芬的体外反应，并与临床预后不良有关。

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Activated Src kinase may contribute to the progression and spread of breast cancers and recent in vitro evidence suggests a role for Src in acquired endocrine resistance. The purpose of this study was to investigate whether modulation of Src activity in endocrine-sensitive and endocrine-resistant breast cancer cells directly affected their phenotype and sensitivity to 4-hydroxy Tamoxifen (tamoxifen) and to determine whether Src activity in breast cancer tissue affected patient outcome. Expression of constitutively active Src in ER-positive, endocrine-sensitive MCF7 breast cancer cells resulted in the development of an aggressive phenotype, akin to that previously observed in cell models of Tamoxifen resistance, and, significantly, attenuated their response to tamoxifen. Conversely, expression of dominant negative-Src in tamoxifen-resistant MCF7 cells resensitized them to tamoxifen. An exploratory immunohistochemical study of an archival primary breast tumor series (n = 75) with parallel clinicopathological data and in normal breast tissues (n = 19) revealed higher levels of activated Src in the cytoplasm (p < 0.01) and lower levels of nuclear Src (p < 0.01) in tumor tissue compared with normal tissue. Whereas elevated levels of activated-Src in the cytoplasm of tumors was significantly associated with reduced survival in ER+ patients (p = 0.031), elevated levels of activated Src within the nucleus appeared to associate with an improved hormonal response. Together these data are further suggestive of a role for Src in breast cancer where it may alter response to endocrine therapy.
机译：活化的Src激酶可能有助于乳腺癌的发展和扩散，最近的体外证据表明Src在获得性内分泌抵抗中起作用。这项研究的目的是调查内分泌敏感和内分泌抗性乳腺癌细胞中Src活性的调节是否直接影响其表型和对4-羟基他莫昔芬（他莫昔芬）的敏感性，并确定乳腺癌组织中Src活性是否影响患者结果。 ER阳性，对内分泌敏感的MCF7乳腺癌细胞中组成型活性Src的表达导致了侵袭性表型的发展，类似于先前在他莫昔芬耐药性细胞模型中观察到的表型，并且显着减弱了它们对他莫昔芬的反应。相反，在他莫昔芬耐药的MCF7细胞中显性负性Src的表达使它们对他莫昔芬重新敏感。一项探索性免疫组织化学研究，对存档的原发性乳腺肿瘤系列（n = 75）进行了平行临床病理学分析，在正常乳腺组织中（n = 19）发现，胞浆中激活的Src水平较高（p <0.01），而核Src水平较低与正常组织相比（p <0.01）。肿瘤细胞质中激活的Src水平升高与ER +患者的存活率降低显着相关（p = 0.031），而细胞核内激活的Src水平升高似乎与荷尔蒙反应改善有关。这些数据加在一起进一步暗示了Src在乳腺癌中的作用，它可能改变对内分泌治疗的反应。

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