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Growth-suppressive effects of BPOZ and EGR2, two genes involved in the PTEN signaling pathway

Oncogene volume 20, pages 4457–4465 (2001)Cite this article

Abstract

Defects in PTEN, a tumor suppressor, have been found in cancers arising in a variety of human tissues. To elucidate the tumor-suppressive function of this gene, we have been analysing expression profiles of cancer cells after introduction of exogenous PTEN. Those experiments identified 99 candidate genes that were transcriptionally transactivated. Among them, we report here the further analyses of eight genes, EGR2/Krox-20, BPOZ, APS, HCLS1/HS1, DUSP1/MKP1, NDRG1/Drg1/RTP, NFIL3/E4BP4, and a novel gene (PINK1, PTEN-induced putative kinase). Expression of six of them (PINK1, EGR2, HCLS1, DUSP1, BPOZ, and NFIL3) was decreased in ovarian tumors compared with corresponding normal tissues. Colony-formation assays using plasmid clones designed to express each gene indicated that EGR2 and BPOZ were able to suppress growth of cancer cells significantly; in particular, cancer-cell lines stably expressing BPOZ grew more slowly than control cells containing mock vector. Flow cytometry suggested that over-expression of BPOZ inhibited progression of the cell cycle at the G1/S transition. Anti-sense oligonucleotides for BPOZ or EGR2 effectively inhibited their expression, and cell growth was accelerated. Therefore both genes appear to be novel candidates as mediators of the PTEN growth-suppressive signaling pathway.

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Acknowledgements

We thank Hiroyuki Kuramoto, Masato Nishida, and Toyomi Satoh for help in obtaining HEC-151, Ishikawa3-H-12, and Sawano, respectively. Mieko Matsushima-Nishiu, Yoichi Furukawa, Kenji Ono, Hideyuki Ishiguro, Manabu Fujita, Yumi Nakajima for helpful advice.

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  1. Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan

    Motoko Unoki & Yusuke Nakamura

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  1. Motoko Unoki
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  2. Yusuke Nakamura
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Correspondence to Yusuke Nakamura.

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Unoki, M., Nakamura, Y. Growth-suppressive effects of BPOZ and EGR2, two genes involved in the PTEN signaling pathway. Oncogene 20, 4457–4465 (2001). https://doi.org/10.1038/sj.onc.1204608

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