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Functional evidence for the presence of tumor suppressor gene on chromosome 10p15 in human prostate cancers

Oncogene volume 20, pages 314–319 (2001)Cite this article

Abstract

Loss of heterozygosity on chromosome 10p was observed frequently in human prostate cancers. Studies have demonstrated that the introduction of the short arm of human chromosome 10 into a human prostate cancer cell line, PPC-1, by microcell-mediated chromosome transfer (MMCT), suppressed the malignant phenotype, suggesting the presence of a prostate tumor suppressor gene(s) within a region of 17 cM at distal 10p. To narrow down the candidate region harboring the tumor suppressor gene, a series of 10p fragments were transferred into PPC-1 cells by MMCT using a panel of hamster–human hybrid cells containing various portions of 10p. Four of the six hybrid cells obtained showed decreased tumorigenicity when injected subcutaneously into athymic nude mice. Tumors developed only at six of 40 injection sites for these four hybrid cells. In contrast, the other two hybrid cells, as well as parental PPC-1 cells, were judged to be fully tumorigenic because tumors appeared at a total 26 of 32 sites for the two hybrid cells and 15 of 16 sites for PPC-1. Allelotyping of 10p combined with fluorescence in situ hybridization in these hybrid cells suggested that a prostate tumor suppressor gene was located within a fragment of approximately 1.2 Mb flanked by D10S1172 and D10S226 on 10p15.1.

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Acknowledgements

We thank Dr Arthur R Brothman for providing PPC-1 cells and Dr Raymond L White for valuable comments and suggestions. This work was supported in part by a Grant-in Aid for the Second Comprehensive 10-Year Strategy for Cancer Control from the Ministry of Health and Welfare, Japan; and by a Grant-in-Aid for Special Projects for Cancer Research from the Ministry of Education, Science, Sports and Culture of Japan. H Fukuhara is a recipient of Research Resident Fellowships from the Foundation for Promotion of Cancer Research of Japan.

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Authors and Affiliations

  1. Tumor Suppression & Functional Genomics Project, National Cancer Center Research Institute, Tokyo, 104-0045, Japan

    Hiroshi Fukuhara, Tomoko Maruyama, Takao Sekiya & Yoshinori Murakami

  2. R&D Center, BML, Kawagoe, 350-1101, Japan

    Sachio Nomura

  3. School of Life Science, Faculty of Medicine, Tottori University, Tottori, 683-8503, Japan

    Mitsuo Oshimura

  4. Department of Urology, University of Tokyo, School of Medicine, Tokyo, 113-8655, Japan

    Tadaichi Kitamura

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  1. Hiroshi Fukuhara
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Fukuhara, H., Maruyama, T., Nomura, S. et al. Functional evidence for the presence of tumor suppressor gene on chromosome 10p15 in human prostate cancers. Oncogene 20, 314–319 (2001). https://doi.org/10.1038/sj.onc.1204079

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