1. A novel protein tyrosine kinase NOK that shares homology with platelet- derived growth factor/fibroblast growth factor receptors induces tumorigenesis and metastasis in nude mice
- Author
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Zhijie Chang, Xin Zi Yu, Yong Ming Ren, Pei La Chen, Ying Hua Li, Yue Chen, Shu Ping Zhang, Shi Dong Wang, Xin-Yuan Fu, Tieshi Li, Lian Xia Song, Li Liu, and Ta Lin Suo
- Subjects
Cancer Research ,Platelet-derived growth factor ,MAP Kinase Signaling System ,medicine.medical_treatment ,Molecular Sequence Data ,Mice, Nude ,Biology ,Fibroblast growth factor ,Transfection ,chemistry.chemical_compound ,Mice ,Phosphatidylinositol 3-Kinases ,Growth factor receptor ,Cell Line, Tumor ,Chlorocebus aethiops ,medicine ,Animals ,Humans ,Neoplasm Invasiveness ,Receptors, Platelet-Derived Growth Factor ,Amino Acid Sequence ,RNA, Messenger ,Cloning, Molecular ,Promoter Regions, Genetic ,Oncogene Proteins ,Sequence Homology, Amino Acid ,Kinase ,Growth factor ,Receptor Protein-Tyrosine Kinases ,Protein-Tyrosine Kinases ,Receptors, Fibroblast Growth Factor ,Cell Transformation, Neoplastic ,Oncology ,chemistry ,Fibroblast growth factor receptor ,Mitogen-activated protein kinase ,COS Cells ,Cancer research ,biology.protein ,NIH 3T3 Cells ,Tyrosine kinase ,Cell Division - Abstract
Receptor protein tyrosine kinases (RPTKs) play important roles in the regulation of a variety of cellular processes including cell migration, proliferation, and protection from apoptosis. Here, we report the identification and characterization of a novel RPTK-like molecule that has a critical role in induction of tumorigenesis and metastasis and is termed Novel Oncogene with Kinase-domain (NOK). NOK contains a putative single transmembrane domain and a conserved intracellular tyrosine kinase domain that shares homology with members of the platelet-derived growth factor/fibroblast growth factor receptor superfamily. NOK was exclusively located in the cytoplasm. NOK mRNAs were detected in limited human organs and expressed with the highest abundance in the prostate. A variety of tumor cells also expressed the NOK mRNAs. We demonstrated that NIH3T3 and BaF3 cells could be strongly transformed by the expression of the NOK gene as examined by colony formation experiment. In addition, BaF3 cells with the stable expression of NOK induced rapid tumorigenesis in nude mice. Interestingly, these NOK-expressing tumor cells could promptly invade and spread into various distinct organs and form metastatic foci, eventually leading to the rapid death of these animals. Moreover, molecular mechanism studies indicated that NOK could concomitantly activate both MAP kinase and phosphatidylinositol 3′-kinases (PI3K) pathways in stable BaF3 cells. Thus, our results both in vitro and in vivo suggest that NOK is a novel oncogene with the capacity of promoting cell transformation, tumorigenesis, and metastasis.
- Published
- 2004