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

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.
AuthorsSoon Young Jang, Sung-Wuk Jang, Jesang Ko
JournalCancer letters (Cancer Lett) Vol. 314 Issue 2 Pg. 185-97 (Jan 28 2012) ISSN: 1872-7980 [Electronic] Ireland
PMID22004728 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2011 Elsevier Ireland Ltd. All rights reserved.
Chemical References
  • CREB3 protein, human
  • Cyclic AMP Response Element-Binding Protein
  • ADP-Ribosylation Factors
  • ARF4 protein, human
  • Tetradecanoylphorbol Acetate
Topics
  • ADP-Ribosylation Factors (genetics)
  • Breast Neoplasms (pathology)
  • Cell Line, Tumor
  • Cell Movement
  • Cyclic AMP Response Element-Binding Protein (genetics, physiology)
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Promoter Regions, Genetic
  • Response Elements
  • Tetradecanoylphorbol Acetate (pharmacology)

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