Study of Mechanism of Down-Regulation of Nucleophosmin/B23 during Retinoic Acid-Induced Differentiation of Human Leukemia Cell Line

• Main Authors: lin hsiu ping, 林琇萍
• Other Authors: Benjamin Y. M. Yung
• Format: Others
• Language: en_US
• Published: 2003
• Online Access: http://ndltd.ncl.edu.tw/handle/78585919365696129824

碩士 === 長庚大學 === 基礎醫學研究所 === 91 === Retinoic acid (RA) triggers terminal differentiation and growth arrest of several established human myeloid cell lines. Although the biologic effects of ATRA are well characterized, the molecular mechanisms regulate these processes are largely unknown. Nucleophosmin/B23 is a major nucleolar phosphoprotein, has been implicated to have a functional role in growth and differentiation control. Nucleophosmin/B23 mRNA and protein are decreased during RA-induced cellular differentiation. NPM/B23 antisense oligomer treatment potentiates RA-induced differentiation. In this study, attempts were therefore made to elucidate how nucleophosmin/B23 was affected by RA and those signaling pathways. Our results showed that RA-induced decrease of nucleophosmin/B23 protein expression is inhibited by MEK inhibitor PD98059 but enhanced by p38 MAP kinase inhiitor SB203580. NPM/B23 promoter activity are up and down-regulated by PD98059 and SB203580. SB203580 potentiates RA-induced decrease of c-myc and YY1 protein level and increase of cellular differentiation. Decreased of NPM/B23 promoter activity by c-myc antisense oligomer. Results of this study suggest MAP and p38 kinase may play positive and negative regulatory effect on NPM/B23 during RA-induced differentiation. And c-myc was also involved in regulation of NPM/B23 gene expression during RA-treated cells.