Synergistic effect of retinoic acid and dehydroepiandrosterone on differentiation of human neuroblastoma cells

FEBS Letters

Silvagno, Francesca¹  Piero Pescarmona, Gian¹  Guarnieri, Vincenzo¹  Capizzi, Anna¹ 

[1] Dipartimento di Genetica, Biologia e Biochimica, Facolta’ di Medicina e Chirurgia, Universita’ di Torino, Sezione di Biochimica, Via Santena 5 bis, 10126 Turin, Italy

关键词: Retinoic acid;    Dehydroepiandrosterone;    Neuroblastoma differentiation;    Proliferation;    Matrix metalloproteinases;    RA;    retinoic acid;    DHEA;    dehydroepiandrosterone;    DHEAS;    dehydroepiandrosterone sulfate;    MMP;    matrix metalloproteinase;    RAR;    retinoic acid receptor;    RXR;    retinoid X receptor;    ER;    estrogen receptor;    GAP-43;    growth-associated protein 43;   

DOI  :  10.1016/S0014-5793(02)03667-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Retinoic acid (RA) affects many cell types by either promoting their survival or inducing their differentiation. Dehydroepiandrosterone (DHEA), a precursor for both androgenic and estrogenic steroids and abundantly produced by brain, is known as an inhibitor of cell proliferation. Differentiation of a human neuroblastoma cell line (SK-N-BE) was evaluated measuring growth rate, motility, neurite extension and GAP-43 expression. We report that DHEA enhances the differentiating effect of RA on neuroblastoma cells via a signalling that is not RA receptor-mediated. Instead, we show a differential expression of matrix metalloproteinases: RA enhances the activity of MMP-2, whereas MMP-9 expression is up-regulated by DHEA. The concerted modulation of these proteinases may support the neurite outgrowth observed after co-treatment with the two drugs.

【 授权许可】

Unknown