Regulation of ADP-ribosylation factor 4 expression by small leucine zipper protein and involvement in breast cancer cell migration

Soon Young Jang, Sung Wuk Jang, Jesang Ko

    Research output: Contribution to journalArticlepeer-review

    29 Citations (Scopus)

    Abstract

    ADP-ribosylation factor 4 (ARF4) is a member of the Ras superfamily of small guanine nucleotide-binding proteins. ARF4 is known to interact with the epidermal growth factor receptor (EGFR) and mediates the EGF-dependent signal pathway, and has an anti-apoptotic function in human glioblastoma-derived U373MG cells. Although ARF4 plays a role in cancer cells, the molecular mechanism underlying regulation of its expression and its exact functions in breast cancer are unknown. In this study, we investigated the regulatory mechanism of ARF4 expression and its involvement in breast cancer cell migration. Our results show that phorbol 12-myristate 13-acetate (PMA) treatment increases ARF4 expression at both the transcriptional and translational levels. We found that the novel transcription factor small leucine zipper protein (sLZIP) binds directly to the CRE motif of the -43 to -35 region in the ARF4 promoter and regulates PMA-induced ARF4 expression. We also found that PMA-stimulated ARF4 expression increases AP-1 promoter activity, leading to induction of breast cancer cell migration. These results indicate that sLZIP-regulated ARF4 expression in response to PMA is involved in breast cancer cell migration, and sLZIP and ARF4 are potential therapeutic target molecules for treating breast cancer invasion and metastasis.

    Original languageEnglish
    Pages (from-to)185-197
    Number of pages13
    JournalCancer letters
    Volume314
    Issue number2
    DOIs
    Publication statusPublished - 2012 Jan 28

    Keywords

    • ARF4
    • Breast cancer
    • Cell migration
    • slZIP

    ASJC Scopus subject areas

    • Oncology
    • Cancer Research

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