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Association of a lung tumor suppressor TSLC1 with MPP3, a human homologue of Drosophila tumor suppressor Dlg

Oncogene volume 22, pages 6160–6165 (2003)Cite this article

An Erratum to this article was published on 15 January 2004

Abstract

We have previously identified the tumor suppressor in lung cancer 1 (TSLC1) gene as a novel tumor suppressor in human non-small cell lung cancer (NSCLC) by functional complementation. TSLC1 encodes a membrane glycoprotein belonging to an immunoglobulin superfamily and participates in cell adhesion. A truncating mutation of the TSLC1 corresponding to its cytoplasmic domain in a primary NSCLC tumor suggests that this domain is important for tumor suppressor activity. Here, we report that TSLC1 directly associates with MPP3, one of the human homologues of a Drosophila tumor suppressor gene, Discs large (Dlg). This interaction was dependent on the presence of a PDZ-binding motif at the carboxyl terminus of TSLC1. Furthermore, TSLC1 and MPP3 were colocalized at the cell–cell attachment sites in both a low and a high cell density. The MPP3 gene was expressed in normal lung as well as in many tissues examined except for peripheral blood lymphocytes but lost its expression in one of the nine NSCLC cell lines. These results suggest that TSLC1 and MPP3 are involved in the same cascade of cell–cell interaction, and that the disruption of this cascade might lead cells to malignant growth and tumor formation in lung cancer.

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Acknowledgements

The authors are grateful to Drs T Yamada and Y Ino for their generous help with the Bio-Rad Radiance 2000 confocal scanning system. This work was partially supported by a Grant-in-Aid for the Second Comprehensive 10-Year Strategy for Cancer Control from the Ministry of Health, Labor, and Welfare of Japan; a Grant-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Culture, Sports, Science, and Technology, Japan; and a Grant from the Promotion of Fundamental Studies in Health Sciences of the Organization for Pharmaceutical Safety and Research (OPSR) of Japan. HF, TF, and MK are recipients of Research Resident Fellowships from the Foundation for Promotion of Cancer Research of Japan, and MM is a recipient of Research Fellowships from OPSR.

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Authors and Affiliations

  1. Tumor Suppression & Functional Genomics Project, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

    Hiroshi Fukuhara, Mari Masvuda, Mika Yageta, Takeshi Fukami, Masami Kuramochi, Tomoko Maruyama & Yoshinori Murakami

  2. Department of Urology, University of Tokyo, School of Medicine, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

    Tadaichi Kitamura

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  1. Hiroshi Fukuhara
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Correspondence to Yoshinori Murakami.

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Fukuhara, H., Masvuda, M., Yageta, M. et al. Association of a lung tumor suppressor TSLC1 with MPP3, a human homologue of Drosophila tumor suppressor Dlg. Oncogene 22, 6160–6165 (2003). https://doi.org/10.1038/sj.onc.1206744

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