Decreased insulin-like growth factor-II/mannose 6-phosphate receptor expression enhances tumorigenicity in JEG-3 cells.
The insulin-like growth factor-II/mannose-6 phosphate receptor (IGF-II/M6PR) is believed to bind and degrade the potent mitogen IGF-II, a growth factor for many tumors. This receptor has been shown to be mutated and/or lost in a significant percentage of a variety of tumors, implying that it may act as a negative regulator of cell growth. In this study, we demonstrate that down-regulation of this receptor, mediated by antisense IGF-II/M6PR cDNA transfection into JEG-3 choriocarcinoma cells, results in increased growth rate in vitro and increased tumor growth rate in vivo. These findings demonstrate that a decrease in IGF-II/M6PR expression results in a growth advantage in JEG-3 cells and are consistent with the hypothesis that the IGF-II/M6PR is an inhibitor of tumor growth.
O'Gorman
D B
DB
Kolling Institute of Medical Research, University of Sydney and Royal North Shore Hospital, St. Leonards, NSW, Australia.
Costello
M
M
Weiss
J
J
Firth
S M
SM
Scott
C D
CD
D000818:Animals; D016375:Antisense Elements (Genetics) / Q000008:administration & dosage* / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D002822:Choriocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015536:Down-Regulation; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D017527:Receptor, IGF Type 2 / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured
D016375:Antisense Elements (Genetics); D017527:Receptor, IGF Type 2