title: SWAP-70 contributes to spontaneous transformation of mouse embryo fibroblasts.
abstract: Mouse embryo fibroblasts (MEFs) grow slowly after cultivation from animals, however, after an extended period of cultivation, their growth accelerates. We found that SWAP-70 deficient MEFs failed to increase growth rates. They maintain normal growth rates and proliferation cycles for at least 5 years. Complementing SWAP-70 deficiency in one of these MEF clones, MEF1F2, by expressing human SWAP-70 resulted in fast growth of the cells after further cultivation for a long period. The resulting cells show a transformation phenotype, since they grow on top of each other and do not show contact inhibition. This phenotype was reverted when sanguinarine, a putative SWAP-70 inhibitor, was added. Two SWAP-70 expressing clones were examined in detail. Even after cell density became very high their cdc2 and NFκB were still activated suggesting that they do not stop growing. One of the clones formed colonies in soft agar and formed tumors in nude mice. Lately, one more clone became transformed being able to make colonies in soft agar. We maintain 4 human SWAP-70 expressing MEF1F2 cell lines. Three out of 4 clones exhibited transforming phenotypes. The mouse SWAP-70 gene also promoted transformation of MEFs. Taken together our data suggest that SWAP-70 is not a typical oncogene, but is required for spontaneous transformation of MEFs.
authors.affiliation: Institute of Cellular and System Medicine National Health Research Institute, Zhunan Town 35053, Miaoli County, Taiwan, ROC.
authors.forename: Yu-Tzu
authors.initials: YT
authors.lastname: Chang
authors.affiliation: Institute of Cellular and System Medicine National Health Research Institute, Zhunan Town 35053, Miaoli County, Taiwan, ROC.
authors.forename: Chung-Li
authors.initials: CL
authors.lastname: Shu
authors.affiliation: Institute of Cellular and System Medicine National Health Research Institute, Zhunan Town 35053, Miaoli County, Taiwan, ROC.
authors.forename: Jing-Yang
authors.initials: JY
authors.lastname: Lai
authors.affiliation: Institute of Cellular and System Medicine National Health Research Institute, Zhunan Town 35053, Miaoli County, Taiwan, ROC.
authors.forename: Ching-Yu
authors.initials: CY
authors.lastname: Lin
authors.affiliation: Institute of Cellular and System Medicine National Health Research Institute, Zhunan Town 35053, Miaoli County, Taiwan, ROC.
authors.forename: Chih-Pin
authors.initials: CP
authors.lastname: Chuu
authors.affiliation: Division of Tumor and Cellular Biochemistry Department of Medical Sciences Faculty of Medicine University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki-shi, Miyazaki 889-1692 Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Morishita
authors.affiliation: Division of Tumor and Cellular Biochemistry Department of Medical Sciences Faculty of Medicine University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki-shi, Miyazaki 889-1692 Japan.
authors.forename: Tomonaga
authors.initials: T
authors.lastname: Ichikawa
authors.affiliation: Faculty of Medicine Carl Gustav Carus, Institute of Physiological Chemistry, Dresden University of Technology, Dresden, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Jessberger
authors.affiliation: Institute of Cellular and System Medicine National Health Research Institute, Zhunan Town 35053, Miaoli County, Taiwan, ROC. Electronic address: 990412@nhri.org.tw.
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Fukui
mesh_terms: D053119:Benzophenanthridines / Q000494:pharmacology; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000473:pathology*; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000473:pathology*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D020662:Guanine Nucleotide Exchange Factors / Q000172:deficiency / Q000378:metabolism*; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D015778:Minor Histocompatibility Antigens / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D009687:Nuclear Proteins / Q000172:deficiency / Q000378:metabolism*; D010641:Phenotype; D013997:Time Factors
chemical_list: D053119:Benzophenanthridines; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D020662:Guanine Nucleotide Exchange Factors; D007546:Isoquinolines; D015778:Minor Histocompatibility Antigens; D016328:NF-kappa B; D009687:Nuclear Proteins; C491873:SWAP70 protein, human; C113365:Swap70 protein, mouse; C005705:sanguinarine; D016203:CDC2 Protein Kinase
keywords: Mouse embryo fibroblasts; SWAP-70; Soft agar colony formation; Transformation; Tumor formation