Differential expression of FAK and Pyk2 in metastatic and non-metastatic EL4 lymphoma cell lines.
Differential expression of FAK and Pyk2 in metastatic and non-metastatic EL4 lymphoma cell lines.
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DOI：
10.1007/s10585-011-9391-y
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发表时间：
2011-08
影响因子：
4
通讯作者：
Meier, Kathryn E.
中科院分区：
文献类型：
--
作者：
Zhang, Zhihong;Knoepp, Stewart M.;Ku, Hsun;Sansbury, Heather M.;Xie, Yuhuan;Chahal, Manpreet S.;Tomlinson, Stephen;Meier, Kathryn E.
关键词：
鼠EL 4淋巴瘤细胞系存在于对佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）敏感或耐药的变体中。在敏感细胞中，PMA导致Erk MAPK活化和Erk介导的生长停滞。在抗性细胞中，PMA诱导低水平的Erk活化，而不生长停滞。表型的一个相对未探索的方面是抗性细胞比敏感细胞更粘附于培养基质。在这项研究中，蛋白酪氨酸激酶FAK和Pyk 2在EL 4表型中的作用进行了检查，特别强调这些蛋白在转移中的作用。FAK仅在PMA抗性（或中间表型）EL 4细胞中表达，与增强的细胞-基质粘附相关，而Pyk 2在非粘附PMA敏感性细胞中更高表达。PMA处理导致PMA敏感性EL 4细胞中FAK（上调）和Pyk 2（下调）的mRNA的调节，但不导致PMA抗性EL 4细胞中FAK和Pyk 2的mRNA的调节。Pyk 2 mRNA的增加与Pyk 2蛋白表达的增加相关。通过转染和敲低实验进一步探讨FAK在细胞表型中的作用。结果表明，FAK在调节PMA诱导的EL 4细胞中Erk活化中不起主要作用。然而，敲除研究表明，FAK表达是PMA抗性细胞增殖和迁移所必需的。在使用同基因小鼠的实验转移模型中，仅表达FAK（PMA抗性）的EL 4细胞形成肝肿瘤。总之，这些研究表明FAK表达促进EL 4淋巴瘤细胞的转移。
The murine EL4 lymphoma cell line exists in variants that are either sensitive or resistant to phorbol 12-myristate 13-acetate (PMA). In sensitive cells, PMA causes Erk MAPK activation and Erk-mediated growth arrest. In resistant cells, PMA induces a low level of Erk activation, without growth arrest. A relatively unexplored aspect of the phenotypes is that resistant cells are more adherent to culture substrate than are sensitive cells. In this study, the roles of the protein tyrosine kinases FAK and Pyk2 in EL4 phenotype were examined, with a particular emphasis on the role of these proteins in metastasis. FAK is expressed only in PMA-resistant (or intermediate phenotype) EL4 cells, correlating with enhanced cell-substrate adherence, while Pyk2 is more highly expressed in non-adherent PMA-sensitive cells. PMA treatment causes modulation of mRNA for FAK (up-regulation) and Pyk2 (down-regulation) in PMA-sensitive but not PMA-resistant EL4 cells. The increase in Pyk2 mRNA is correlated with an increase in Pyk2 protein expression. The roles of FAK in cell phenotype were further explored using transfection and knockdown experiments. The results showed that FAK does not play a major role in modulating PMA-induced Erk activation in EL4 cells. However, the knockdown studies demonstrated that FAK expression is required for proliferation and migration of PMA-resistant cells. In an experimental metastasis model using syngeneic mice, only FAK-expressing (PMA-resistant) EL4 cells form liver tumors. Taken together, these studies suggest that FAK expression promotes metastasis of EL4 lymphoma cells.
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影响因子：
20.3
作者：
Hatch, WC;Ganju, RK;Groopman, JE
通讯作者：
Groopman, JE
DOI：
10.3390/ph3072045
发表时间：
2010-07-02
期刊：
Pharmaceuticals (Basel, Switzerland)
影响因子：
--
作者：
Chahal MS;Brauner DJ;Meier KE
通讯作者：
Meier KE
影响因子：
4.8
作者：
Andreev, J;Galisteo, ML;Schlessinger, J
通讯作者：
Schlessinger, J
DOI：
10.1016/j.bbaexp.2004.03.002
发表时间：
2004-05-25
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION
影响因子：
--
作者：
Golubovskaya, V;Kaur, A;Cance, W
通讯作者：
Cance, W
影响因子：
20.3
作者：
Aoudjit, F;Vuori, K
通讯作者：
Vuori, K