Ing4 induces Cell Growth Inhibition in Human Lung Adenocarcinoma A549 Cells by Means of Wnt-1/β-Catenin Signaling Pathway

Authors

  • Xiaomei Li,

    1. Department of Pathology, the Affiliated First Harbin Medical University, Harbin, China
    2. Department of Pathology, the Affiliated Tumor Hospital of Harbin Medical University, Harbin, China
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    • Drs. Li and Cai contributed equally to this work.

  • Limin Cai,

    1. Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical University, Nanjing, China
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    • Drs. Li and Cai contributed equally to this work.

  • Meihua Liang,

    1. Department of Endocrinology, the Affiliated Secondary Hospital of Harbin Medical University, Harbin, China
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  • Yandong Wang,

    1. Department of Dermatology, Daqing Longnan Hospital, Daqing, China
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  • Jing Yang,

    1. Department of Dermatology, Heilongjiang province Hospital, Harbin, China
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  • Yulan Zhao

    Corresponding author
    1. Department of Pathology, the Affiliated First Harbin Medical University, Harbin, China
    • Department of Pathology, the Affiliated Tumor Hospital of Harbin Medical University, 246 Haping Road, Harbin, China, 150040
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    • Fax: 86-451-65295522.


Abstract

ING4, as a novel candidate tumor suppressor gene, has been implicated in several human malignances by tumor growth inhibition and apoptosis enhancement. The mechanism of ING4 remains largely unknown. The purpose of this study was to investigate the inhibitory tumor growth effects of ING4 on lung adenocarcinoma, and its mechanism, by ING4 cDNA transduction into A549 cells. Furthermore, the expression level of ING4 in lung adenocarcinoma tissues was examined. The expression of ING4 was markedly reduced in human lung adenocarcinoma tissues. Overexpression of ING4 can induce growth inhibition in A549 cells both in vitro and in vivo, and also induce up-regulation of p27, down-regulation of cyclinD1, SKP2, and Cox2, and inactivation of the Wnt-1/β-catenin pathway. Moreover, overexpression of ING4 can enhance the sensitivity of A549 cells to radiotherapy and chemotherapy. Thus, ING4 may play an inhibitory role on A549 cell proliferation and tumor growth in lung adenocarcinoma by up-regulation or down-regulation of cell proliferation-regulating proteins such as p27, cyclinD1, SKP2, and Cox2 by means of inactivation of Wnt-1/β-catenin signaling. Anat Rec, 291:593–600, 2008. © 2008 Wiley-Liss, Inc.

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