Expression of HER2 and estrogen receptor α depends upon nuclear localization of Y-box binding protein-1 in human breast cancers

Teruhiko Fujii, Akihiko Kawahara, Yuji Basaki, Satoshi Hattori, Kazutaka Nakashima, Kenji Nakano, Kazuo Shirouzu, Kimitoshi Kohno, Takashi Yanagawa, Hideaki Yamana, Kazuto Nishio, Mayumi Ono, Michihiko Kuwano, Masayoshi Kage

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    Abstract

    In our present study, we examined whether nuclear localization of Y-box binding protein-1 (YB-1) is associated with the expression of epidermal growth factor receptors (EGFR), hormone receptors, and other molecules affecting breast cancer prognosis. The expression of nuclear YB-1, clinicopathologic findings, and molecular markers [EGFR, HER2, estrogen receptor (ER)α, ERβ, progesterone receptor, chemokine (C-X-C motif) receptor 4 (CXCR4), phosphorylated Akt, and major vault protein/lung resistance protein] were immunohistochemically analyzed. The association of the expression of nuclear YB-1 and the molecular markers was examined in breast cancer cell lines using microarrays, quantitative real-time PCR, and Western blot analyses. Knockdown of YB-1 with siRNA significantly reduced EGFR, HER2, and ERA expression in ERα-positive, but not ERα-negative, breast cancer cell lines. Nuclear YB-1 expression was positively correlated with HER2 (P = 0.0153) and negatively correlated with ERα (P = 0.0122) and CXCR4 (P = 0.0166) in human breast cancer clinical specimens but was not correlated with EGFR expression. Nuclear YB-1 expression was an independent prognostic factor for overall (P = 0.0139) and progression-free (P = 0.0280) survival. In conclusion, nuclear YB-1 expression might be essential for the acquisition of malignant characteristics via HER2-Akt-dependent pathways in breast cancer patients. The nuclear localization of YB-1 could be an important therapeutic target against not only multidrug resistance but also tumor growth dependent on HER2 and ERα.

    Original languageEnglish
    Pages (from-to)1504-1512
    Number of pages9
    JournalCancer Research
    Volume68
    Issue number5
    DOIs
    Publication statusPublished - Mar 1 2008

    Fingerprint

    Estrogen Receptors
    Breast Neoplasms
    Y-Box-Binding Protein 1
    CCR Receptors
    Cell Line
    Multiple Drug Resistance
    Progesterone Receptors
    Small Interfering RNA
    human YBX1 protein
    Real-Time Polymerase Chain Reaction
    Western Blotting
    Hormones
    Survival
    ErbB Receptors
    Growth
    Neoplasms
    major vault protein

    All Science Journal Classification (ASJC) codes

    • Oncology
    • Cancer Research

    Cite this

    Expression of HER2 and estrogen receptor α depends upon nuclear localization of Y-box binding protein-1 in human breast cancers. / Fujii, Teruhiko; Kawahara, Akihiko; Basaki, Yuji; Hattori, Satoshi; Nakashima, Kazutaka; Nakano, Kenji; Shirouzu, Kazuo; Kohno, Kimitoshi; Yanagawa, Takashi; Yamana, Hideaki; Nishio, Kazuto; Ono, Mayumi; Kuwano, Michihiko; Kage, Masayoshi.

    In: Cancer Research, Vol. 68, No. 5, 01.03.2008, p. 1504-1512.

    Research output: Contribution to journalArticle

    Fujii, T, Kawahara, A, Basaki, Y, Hattori, S, Nakashima, K, Nakano, K, Shirouzu, K, Kohno, K, Yanagawa, T, Yamana, H, Nishio, K, Ono, M, Kuwano, M & Kage, M 2008, 'Expression of HER2 and estrogen receptor α depends upon nuclear localization of Y-box binding protein-1 in human breast cancers', Cancer Research, vol. 68, no. 5, pp. 1504-1512. https://doi.org/10.1158/0008-5472.CAN-07-2362
    Fujii, Teruhiko ; Kawahara, Akihiko ; Basaki, Yuji ; Hattori, Satoshi ; Nakashima, Kazutaka ; Nakano, Kenji ; Shirouzu, Kazuo ; Kohno, Kimitoshi ; Yanagawa, Takashi ; Yamana, Hideaki ; Nishio, Kazuto ; Ono, Mayumi ; Kuwano, Michihiko ; Kage, Masayoshi. / Expression of HER2 and estrogen receptor α depends upon nuclear localization of Y-box binding protein-1 in human breast cancers. In: Cancer Research. 2008 ; Vol. 68, No. 5. pp. 1504-1512.
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    AU - Kawahara, Akihiko

    AU - Basaki, Yuji

    AU - Hattori, Satoshi

    AU - Nakashima, Kazutaka

    AU - Nakano, Kenji

    AU - Shirouzu, Kazuo

    AU - Kohno, Kimitoshi

    AU - Yanagawa, Takashi

    AU - Yamana, Hideaki

    AU - Nishio, Kazuto

    AU - Ono, Mayumi

    AU - Kuwano, Michihiko

    AU - Kage, Masayoshi

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    N2 - In our present study, we examined whether nuclear localization of Y-box binding protein-1 (YB-1) is associated with the expression of epidermal growth factor receptors (EGFR), hormone receptors, and other molecules affecting breast cancer prognosis. The expression of nuclear YB-1, clinicopathologic findings, and molecular markers [EGFR, HER2, estrogen receptor (ER)α, ERβ, progesterone receptor, chemokine (C-X-C motif) receptor 4 (CXCR4), phosphorylated Akt, and major vault protein/lung resistance protein] were immunohistochemically analyzed. The association of the expression of nuclear YB-1 and the molecular markers was examined in breast cancer cell lines using microarrays, quantitative real-time PCR, and Western blot analyses. Knockdown of YB-1 with siRNA significantly reduced EGFR, HER2, and ERA expression in ERα-positive, but not ERα-negative, breast cancer cell lines. Nuclear YB-1 expression was positively correlated with HER2 (P = 0.0153) and negatively correlated with ERα (P = 0.0122) and CXCR4 (P = 0.0166) in human breast cancer clinical specimens but was not correlated with EGFR expression. Nuclear YB-1 expression was an independent prognostic factor for overall (P = 0.0139) and progression-free (P = 0.0280) survival. In conclusion, nuclear YB-1 expression might be essential for the acquisition of malignant characteristics via HER2-Akt-dependent pathways in breast cancer patients. The nuclear localization of YB-1 could be an important therapeutic target against not only multidrug resistance but also tumor growth dependent on HER2 and ERα.

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