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The PMAIP1 Gene on Chromosome 18 is a Candidate Tumor Suppressor Gene in Human Pancreatic Cancer

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Abstract

Frequent loss of heterozygosity on the long arm of chromosome 18 is observed in pancreatic cancer. Previous studies suggested the existence of one or more tumor-suppressor genes other than SMAD4 on chromosome 18. To identify the candidate tumor-suppressor gene(s), we compared gene expression by cDNA microarray analyses using a pancreatic cancer cell line Panc-1 and its hybrid cell lines showing suppressed cell growth after introduction of one normal copy of chromosome 18. The microarray analyses identified 38 genes on chromosome 18 that showed differential expressional levels. Among these genes, phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1/APR/NOXA) was identified as one of the candidates for tumor suppressor. Expression vector-mediated introduction of PMAIP1 suppressed cell proliferation, and RNAi-mediated knockdown of PMAIP1 induced recovery of cell growth. These results suggest that PMAIP1 may play an important role in the progression of pancreatic cancer.

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Acknowledgments

We are grateful to Dr B.L.S. Pierce (University of Maryland University College) for editorial work in the preparation of this manuscript. This work was supported in part by Grants-in-Aid and the 21st Century COE Program Special Research Grant from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and by a Grant-in-Aid for Cancer Research from the Ministry of Health, Labour and Welfare of Japan.

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  1. Makoto Sunamura

    Present address: Cancer Surgery Section, Hammersmith Hospital, Imperial College, London, UK

Authors and Affiliations

  1. Department of Molecular Pathology, Tohoku University School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan

    Masaharu Ishida, Makoto Sunamura, Toru Furukawa, Liviu P. Lefter & Akira Horii

  2. Department of Gastroenterological Surgery, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan

    Masaharu Ishida, Makoto Sunamura, Liviu P. Lefter, Rina Morita, Masanori Akada, Shinichi Egawa & Michiaki Unno

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  1. Masaharu Ishida
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Correspondence to Akira Horii.

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Ishida, M., Sunamura, M., Furukawa, T. et al. The PMAIP1 Gene on Chromosome 18 is a Candidate Tumor Suppressor Gene in Human Pancreatic Cancer. Dig Dis Sci 53, 2576–2582 (2008). https://doi.org/10.1007/s10620-007-0154-1

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  • DOI: https://doi.org/10.1007/s10620-007-0154-1

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