Interferon‐α inhibits chromogranin A promoter activity in neuroendocrine pancreatic cancer cells

FEBS Letters

Riecken, Ernst-Otto³  Wiedenmann, Bertram²  Rosewicz, Stefan²  Höcker, Michael²  Plath, Thomas²  Wang, Timothy C.¹ 

[1] Gastrointestinal Unit and Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA;Medizinische Klink mit Schwerpunkt Hepatologie und Gastroenterologie, Universitätsklinikum Charité, Campus Virchow-Klinikum, Humboldt Universität, Augustenburger Platz 1, 13353 Berlin, Germany;Medizinische Klinik I, Gastroenterologie und Infektiologie, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, Berlin, Germany

关键词: Neuroendocrine tumor;    Chromogranin A gene regulation;    Hypersecretion syndrome;    Interferon-α;    cAMP-responsive element binding protein;    cAMP-responsive element binding protein binding protein;    mCgA;    mouse chromogranin A;    IFN-α;    interferon-α;    CRE;    cyclic AMP-responsive element;    CREB;    cyclic AMP-responsive element binding protein;    pCREB;    phospho CREB;    CBP;    CREB binding protein;    PMA;    phorbol 12-myristate 13-acetate;    PKC;    protein kinase C;    PKA;    protein kinase A;   

DOI  :  10.1016/S0014-5793(99)01187-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Interferon-α (IFN-α) treatment can suppress the hypersecretion syndrome associated with functional neuroendocrine tumors. Chromogranin A (CgA) is a matrix protein of neuroendocrine secretory vesicles and appears to be essential for an appropriate neuroendocrine secretory function. To test the hypothesis that IFN-α can directly interfere with CgA gene transcription, we performed transient transfection studies in pancreatic neuroendocrine tumor cells employing CgA-luciferase reporter gene constructs showing that IFN-α inhibited basal and protein kinase C-dependent CgA promoter activity. Using 5′-deletion constructs in combination with mutational analysis of the proximal CgA core promoter, a cyclic AMP response element (CRE) at −71 to −64 bp was identified as the IFN-α response element of the CgA gene. Furthermore, functional studies indicated that IFN-α exerts its effect on the CgA promoter via interference with CRE binding protein (CREB)/CREB binding protein (CBP)-dependent transactivation of the CgA-CRE.

【 授权许可】

Unknown