All-trans-retinoic acid-induced growth suppression of blastemal Wilms' tumor.
All-trans-retinoic acid (RA) has been used to suppress growth of malignant cells and induce epithelial differentiation. We investigated whether RA had a similar effect on Wilms' tumor, a childhood tumor of the kidney that arises from the undifferentiated metanephric blastema. W13 cells, a cell line derived from a blastemal Wilms' tumor, were exposed to RA (10(-9)-10(-5) M) and its effects on cell proliferation, gene expression, and differentiation were examined. Treatment of W13 cells with RA resulted in a dose-dependent suppression of growth. Changes in expression of selected genes were determined by Northern analysis. After 24 h, there was a marked dose-dependent down-regulation of N-myc mRNA as well as up-regulation of insulin-like growth factor-II (IGF-II) mRNA. [125I]IGF-II ligand blotting of conditioned medium from RA-treated cultures revealed a dramatic alteration in the pattern of expression of insulin-like growth factor binding proteins (IGFBPs). Examination of RA-treated W13 cultures by light and electron microscopy did not reveal appreciable morphological changes. We conclude that RA inhibits growth and alters gene expression of W13 cells without inducing epithelial differentiation. The modulation of expression of IGF-II, IGFBP, and N-myc may play a role in RA-induced growth suppression of Wilms' tumor cells.
Vincent
T S
TS
Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston 29425, USA.
Re
G G
GG
Hazen-Martin
D J
DJ
Tarnowski
B I
BI
Willingham
M C
MC
Garvin
A J
AJ
D002454:Cell Differentiation / Q000187:drug effects; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D007335:Insulin-Like Growth Factor II / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D007680:Kidney Neoplasms / Q000145:classification / Q000188:drug therapy; D016271:Proto-Oncogene Proteins c-myc / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D014212:Tretinoin / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured; D009396:Wilms Tumor / Q000145:classification* / Q000188:drug therapy*
D018969:Insulin-Like Growth Factor Binding Proteins; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D014212:Tretinoin; D007335:Insulin-Like Growth Factor II