Carcinogenesis Advance Access published online on August 1, 2003
Carcinogenesis, doi:10.1093/carcin/bgg113
© 2003 by Oxford University Press
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CARCINOGENESIS
1 Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science, Yamazaki 2641, Noda-shi, Chiba 278-8510, Japan
* Corresponding author. E-mail: ftashir{at}rs.noda.tus.ac.jp.
Received 20 April 2002
; revised 17 June 2003
; accepted 24 June 2003
The 14-3-3 family proteins are key regulators of various signal transduction pathways including malignant transformation. Previously, we found that the expression of 14-3-3
Forced expression of antisense 14-3-3
RNA suppresses tumor cell growth in vitro and in vivo
2 Division of Tumor Pathology, Kanagawa Cancer Center Research Institute, Nakao 1-1-2, Asahi-ku, Yokohama 241-0815, Japan
3 Division of Biophysics, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
4 Department of Second Division of Pathology, Yokohama City University School of Medicine, Fukuura 3-9, Kanazawa-ku, Yokohama 236-0004, Japan
gene is deregulated as well as c-myc gene in aflatoxin B1 (AFB1)-induced rat hepatoma K1 and K2 cells. To elucidate the implication of 14-3-3 in tumor cell growth, in this paper we analyzed the effect of forced expression of antisense 14-3-3 RNA on the growth and tumorigenicity of K2 cells. K2 cells transfected with antisense 14-3-3 cDNA expression vector diminished their growth ability in monolayer culture and in semi-solid medium. Expression level of vascular endothelial growth factor (VEGF) mRNA was also reduced in these transfectants. Tumors that formed by the transfectants in nude mice were much smaller and histologically more benign tumors, because of their decreased level of mitosis compared with those of the parental cells. Frequency of apoptosis detected by TUNEL assay was increased in the transfectant-derived tumors accompanying the inhibition of angiogenesis. In addition, over-expression of 14-3-3 mRNA was observed in various murine tumor cell lines. These results suggest that 14-3-3 gene plays a pivotal role in abnormal growth of tumor cells in vitro and in vivo.
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