Differential expression of FAK and Pyk2 in metastatic and non-metastatic EL4 lymphoma cell lines
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Zhihong Zhang Stewart M. Knoepp Hsun Ku Heather M. Sansbury Yuhuan Xie Manpreet S. Chahal Stephen Tomlinson Kathryn E. Meier
- چاپ و سال / کشور: 2011
Description
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 nonadherent 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.
Clin Exp Metastasis (2011) 28:551–565 DOI 10.1007/s10585-011-9391-y Received: 5 January 2011 / Accepted: 17 April 2011 / Published online: 1 May 2011
