Accumulation of hRad9 protein in the nuclei of nonsmall cell lung carcinoma cells

Authors

  • Yoshimasa Maniwa M.D.,

    1. Division of Cardiovascular, Thoracic, and Pediatric Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
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  • Masahiro Yoshimura M.D.,

    Corresponding author
    1. Division of Cardiovascular, Thoracic, and Pediatric Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
    • Department of Cardiovascular and Respiratory Surgery, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan
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    • Fax: (011) 81-78-382-5959

  • Vladimir P. Bermudez Ph.D.,

    1. Molecular Biology Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York City, New York
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  • Takeshi Yuki M.D.,

    1. Division of Cardiovascular, Thoracic, and Pediatric Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
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  • Kenji Okada M.D.,

    1. Division of Cardiovascular, Thoracic, and Pediatric Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
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  • Naoki Kanomata M.D.,

    1. Division of Pathology, Kobe University Hospital, Kobe University Graduate School of Medicine, Kobe, Japan
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  • Chiho Ohbayashi M.D.,

    1. Division of Pathology, Kobe University Hospital, Kobe University Graduate School of Medicine, Kobe, Japan
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  • Yoshitake Hayashi M.D.,

    1. Division of Molecular Medicine and Medical Genetics, International Center for Medical Research and Treatment (ICMRT), Kobe University Graduate School of Medicine, Kobe, Japan
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  • Jerard Hurwitz Ph.D.,

    1. Molecular Biology Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York City, New York
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    • Jerard Hurwitz is an American Cancer Society Professor of Molecular Biology.

  • Yutaka Okita M.D.

    1. Division of Cardiovascular, Thoracic, and Pediatric Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
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Abstract

BACKGROUND

DNA damage sensor proteins have received much attention as upstream components of the DNA damage checkpoint signaling pathway that are required for cell cycle control and the induction of apoptosis. Deficiencies in these proteins are directly linked to the accumulation of gene mutations, which can induce cellular transformation and result in malignant disease.

METHODS

Using 48 sets of tumor tissue specimens and peripheral normal lung tissue specimens from 48 patients with nonsmall cell lung carcinoma (NSCLC) who underwent surgery, the authors investigated the expression of hRad9 protein, a member of the human DNA damage sensor family, using immunohistochemical and Western blot analyses.

RESULTS

Immunohistochemical analysis detected the accumulation of hRad9 in the nuclei of tumor cells in 16 tumor tissue specimens, (33% of tumor tissue specimens examined). Western blot analysis also revealed elevated levels of phosphorylated hRad9 protein in NSCLC cells that was accompanied by the detection of phosphorylated Chk1, a protein kinase that regulates the downstream signaling of the DNA damage checkpoint pathway. Furthermore, strong expression of hRad9 was correlated with an increase in Ki-67 expression index in the tumor cells that were examined.

CONCLUSIONS

The findings made in the current study suggest that Rad9 expression may play an important role in cell cycle control in NSCLC cells and may influence NSCLC cell phenotype. Cancer 2005. © 2004 American Cancer Society.

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