mRNA expression patterns of insulin-like growth factor system components in human neuroendocrine tumours.
BACKGROUND
Insulin-like growth factors (IGF) and their corresponding receptors and binding proteins are important in carcinogenesis for several tumours, but their expression pattern in the functionally and biologically heterogeneous human neuroendocrine tumours of the gastroenteropancreatic tract is largely unknown.


METHODS
This study searched for the mRNA expression patterns of components of the IGF system: IGF-1 and IGF-2, IGF receptors 1 and 2 (IGF-1R, IGF-2R), IGF-binding proteins 1-6 (IGFBP1-6)) in the most frequent human gastroenteropancreatic neuroendocrine tumours (gastrinomas, insulinomas, tumours associated with carcinoid syndrome and functionally inactive tumours) employing reverse transcriptase-polymerase chain reaction (RT-PCR).


RESULTS
In the 37 tumour samples analysed (nine gastrinomas, 10 insulinomas, nine tumours associated with carcinoid syndrome and nine functionally inactive tumours) IGFBP-2 was found in all tumour samples while the IGFBP-1 was expressed only at low frequency (10-22%) among the four tumour types. The IGF-2R was predominantly expressed in gastrinomas. Among the four tumour types the expression of IGF-1R, IGF-2R and IGFBP-6 varied significantly. In addition, 12 pairs of significantly coexpressed IGF system components were detected (IGF-1 <--> IGF-1R, IGF-1 <--> IGF-2R, IGF-1 <--> IGFBP-3, IGF-1 <--> IGFBP-6, IGFBP-3 <--> IGF-1R, IGFBP-6 <--> IGF-1R, IGFBP-1 <--> IGF-2R, IGFBP-3 <--> IGF-2R, IGFBP-5 <--> IGF-2R, IGFBP-3 <--> IGFBP-5, IGFBP-3 <--> IGFBP-6, IGFBP-5 <--> IGFBP-6).


CONCLUSIONS
The described differences of the expression patterns of the IGF system components in neuroendocrine tumour subtypes suggest tumour type-dependent different pathways in tumour growth control by IGF system components.
Wulbrand
U
U
Department of Internal Medicine, Philipps-University Marburg, Germany. ulrich.wulbrand@uni-tuebingen.de
Remmert
G
G
Zöfel
P
P
Wied
M
M
Arnold
R
R
Fehmann
H C
HC
D015408:Gastrinoma / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000235:genetics / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000235:genetics / Q000378:metabolism*; D007340:Insulinoma / Q000235:genetics / Q000378:metabolism; D018358:Neuroendocrine Tumors / Q000235:genetics / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism*; D017527:Receptor, IGF Type 2 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013223:Statistics as Topic
D018969:Insulin-Like Growth Factor Binding Proteins; D012333:RNA, Messenger; D017527:Receptor, IGF Type 2; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D017526:Receptor, IGF Type 1