MUC1 contributes to BPDE-induced human bronchial epithelial cell transformation through facilitating EGFR activation.
MUC1 contributes to BPDE-induced human bronchial epithelial cell transformation through facilitating EGFR activation.
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DOI：
10.1371/journal.pone.0033846
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Lin Y
中科院分区：
文献类型：
--
作者：
Xu X;Bai L;Chen W;Padilla MT;Liu Y;Kim KC;Belinsky SA;Lin Y
尽管众所周知表皮生长因子受体（EGFR）参与肺癌进展，但EGFR是否有助于肺上皮细胞转化尚不清楚。粘蛋白1（MUC 1在人类和动物），气道粘液的糖蛋白成分，是过度表达在肺肿瘤;然而，它的作用和潜在的机制在早期肺癌的发生仍然是难以捉摸的。这项研究提供了强有力的证据，证明EGFR和MUC 1参与支气管上皮细胞转化。MUC 1表达的敲低显著降低了苯并[a]芘二醇环氧化物（BPDE）诱导的永生化人支气管上皮细胞的转化，BPDE是香烟烟雾（CS）致癌物苯并（a）芘（BaP）的活性形式。BPDE暴露强烈激活由EGFR、Akt和ERK组成的通路，阻断该通路显著增加BPDE诱导的细胞死亡并抑制细胞转化。MUC 1表达的抑制导致EGFR不稳定和抑制BPDE诱导的Akt和ERK的激活以及细胞毒性的增加。这些结果强烈提示EGFR在BPDE诱导的转化中的重要作用，并证实MUC 1参与肺癌的发展，至少部分地通过介导致癌物诱导的EGFR介导的细胞存活途径的激活来促进细胞转化。
Although it is well known that epidermal growth factor receptor (EGFR) is involved in lung cancer progression, whether EGFR contributes to lung epithelial cell transformation is less clear. Mucin 1 (MUC1 in human and Muc1 in animals), a glycoprotein component of airway mucus, is overexpressed in lung tumors; however, its role and underlying mechanisms in early stage lung carcinogenesis is still elusive. This study provides strong evidence demonstrating that EGFR and MUC1 are involved in bronchial epithelial cell transformation. Knockdown of MUC1 expression significantly reduced transformation of immortalized human bronchial epithelial cells induced by benzo[a]pyrene diol epoxide (BPDE), the active form of the cigarette smoke (CS) carcinogen benzo(a)pyrene (BaP)s. BPDE exposure robustly activated a pathway consisting of EGFR, Akt and ERK, and blocking this pathway significantly increased BPDE-induced cell death and inhibited cell transformation. Suppression of MUC1 expression resulted in EGFR destabilization and inhibition of the BPDE-induced activation of Akt and ERK and increase of cytotoxicity. These results strongly suggest an important role for EGFR in BPDE-induced transformation, and substantiate that MUC1 is involved in lung cancer development, at least partly through mediating carcinogen-induced activation of the EGFR-mediated cell survival pathway that facilitates cell transformation.
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影响因子：
4.7
作者：
Chen, Wenshu;Wang, Xia;Lin, Yong
通讯作者：
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影响因子：
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作者：
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DOI：
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发表时间：
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