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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1998-1-20
pubmed:abstractText
Neuroblastoma cells are thought to depend upon autocrine stimulation by IGF-II but not by IGF-I. We have studied the expression of IGF, IGFBP and IGF receptor mRNA in two human neuroblastoma cell lines, SK-N-MC and CHP, and asked whether or not the expression of the IGF system in these malignant cells determines their growth pattern. SK-N-MC cells grow with a cell doubling time of 36 hours in medium supplemented with 10% fetal calf serum whereas CHP cells only grow with a doubling time of 72 h. In addition, the SK-N-MC cell line has a plating efficiency ten times greater than the CHP cell line. RNase protection assays were performed using (32)P-labelled riboprobes and RNA that had been purified from SK-N-MC and CHP cells respectively. A 520 bases human IGF-I, a 556 bases human IGF-II, a 480 bases human IGF-I receptor and a 250 human IGF-II/mannose-6-phosphate (M6P) receptor probe were radiolabelled as were human IGFBP-1, -2, -3, -4, -5 and -6 probes. While both SKNMC and CHP neuroblastoma cells expressed mRNAs for IGFBP-2, -4, and -6 no signal was detected for IGFBP-1, and -3 and only SK-N-MC cells expressed IGFBP-5 mRNA. In addition, a 400 bases protected band was seen with the IGF-I receptor probe and a 260 bases protected band with the IGF-IIM6P receptor probe in either cell line. Interestingly, a 300 bases protected species was detected with the IGF-II probe in CHP cell RNA whereas SK-N-MC cells did not express IGF-II transcripts. Conversely, SK-N-MC cells expressed a 520 bases IGF-I transcript while CHP cells did not show IGF-I mRNA expression. As determined by specific radioimmunoassays SK-N-MC cells secreted 0.75+/-0.02 ng/ml IGF-I, 1.2+/-0.04 ng/ml IGF-II and 149+/-2.1 ng/ml IGFBP-2 within 24 h, whereas CHP cells secreted 0.1+/-0.01 ng/ml IGF-I, but 6.2+/-0.1ng/ml IGF-II and 254.8+/-5.5 ng/ml IGFBP-2 (N=5). IGFBP-2 secretion correlated positively with IGF-II secretion in CHP cells (r=0.85, P=0.05) and negatively with IGF-I (r= -0.9, P<0.01) in SK-N-MC cells. In conclusion, SK-N-MC cells which grow rapidly and have a high plating efficiency, express IGF-I, while CHP cells that grow more slowly express IGF-II. We hypothesize that neuroblastoma cells depend upon autocrine stimulation by either IGF-I or IGF-II. Variable sensitivity to growth inhibitors or apoptotic processes may be related to the differential expression of the IGF system.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0167-0115
pubmed:author
pubmed:issnType
Print
pubmed:day
26
pubmed:volume
72
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
19-29
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:9404729-Autocrine Communication, pubmed-meshheading:9404729-Blotting, Western, pubmed-meshheading:9404729-Cell Division, pubmed-meshheading:9404729-Culture Media, Conditioned, pubmed-meshheading:9404729-DNA, Complementary, pubmed-meshheading:9404729-Electrophoresis, Polyacrylamide Gel, pubmed-meshheading:9404729-Gene Expression Regulation, Neoplastic, pubmed-meshheading:9404729-Humans, pubmed-meshheading:9404729-Insulin-Like Growth Factor Binding Proteins, pubmed-meshheading:9404729-Insulin-Like Growth Factor I, pubmed-meshheading:9404729-Insulin-Like Growth Factor II, pubmed-meshheading:9404729-Neuroblastoma, pubmed-meshheading:9404729-RNA, Messenger, pubmed-meshheading:9404729-Radioimmunoassay, pubmed-meshheading:9404729-Receptor, IGF Type 1, pubmed-meshheading:9404729-Ribonucleases, pubmed-meshheading:9404729-Tumor Cells, Cultured
pubmed:year
1997
pubmed:articleTitle
Human neuroblastoma cells use either insulin-like growth factor-I or insulin-like growth factor-II in an autocrine pathway via the IGF-I receptor: variability of IGF, IGF binding protein (IGFBP) and IGF receptor gene expression and IGF and IGFBP secretion in human neuroblastoma cells in relation to cellular proliferation.
pubmed:affiliation
Children's Hospital, Justus Liebig University of Giessen, Germany. wieland.kiess@paediat.med.uni-giessen.de
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't