RETINOIC ACID REGULATES INSULIN-LIKE GROWTH FACTOR-II EXPRESSION IN A NEUROBLASTOMA CELL-LINE

被引:35
作者
MATSUMOTO, K
GAETANO, C
DAUGHADAY, WH
THIELE, CJ
机构
[1] NCI, DIV CANC TREATMENT, PEDIAT BRANCH, MOLEC GENET SECT, BETHESDA, MD 20892 USA
[2] WASHINGTON UNIV, SCH MED, DEPT INTERNAL MED, ST LOUIS, MO 63110 USA
关键词
D O I
10.1210/en.130.6.3669
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Insulin-like growth factors (IGF-I and IGF-II) are mitogenic polypeptides that play an important role in normal growth and development. IGF-II has been shown to stimulate the growth of neuroblastoma tumors in an autocrine and paracrine fashion. Critical in determining the role of IGF-II in tumorigenesis is the necessity to delineate factors affecting the transcription of IGF-II in normal and tumor tissues. To date such factors are poorly characterized. In this study we find that retinoic acid (RA), a naturally occurring morphogen, that has been shown to be indispensable in the development of the chick limb bud, stimulates an increase in IGF-II messenger RNA (mRNA) in the Lan-1-15N neuroblastoma cell line. This increase in IGF-II is coincident with RA mediated inhibition of DNA synthesis. An increase in the steady state levels of IGF-II mRNA is detectable within 2 h of RA treatment and maximal by 24 h. In RA-treated Lan-1-15N cells, IGF-II mRNA levels are regulated at the level of new gene transcription and result in an increase in IGF-II protein in the culture supernatant. These studies suggest one mechanism affecting the production of IGF-II in vivo may be mediated by RA and detail a model system by which transcriptional regulation of IGF-II mRNA can be analyzed.
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页码:3669 / 3676
页数:8
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