Overexpression of the insulin-like growth factor I receptor in human pheochromocytomas.
In order to determine the role of the IGF-I receptor (IGF-IR) in human pheochromocytomas we have compared the expression of the IGF-IR in normal tissues and in pheochromocytomas with regard to the IGF-IR mRNA levels and ligand binding. By semiquantitative reverse transcription polymerase chain reaction (RT-PCR), the mRNA of the IGF-IR could be detected in all samples of normal adrenomedullary cells (n = 13) and pheochromocytomas (n = 16). However, pheochromocytomas exhibited 2.8-fold higher mean IGF-IR mRNA levels than normal adrenomedullary cells (2.8 +/- 0.5 x 10(5) molecules/mug RNA vs 7.8 +/- 1.2 x 10(5) molecules/mug RNA; P < 0.001). This overexpression of the IGF-IR in pheochromocytomas could be confirmed at the protein level by binding studies. Radioligand assays and Scatchard analysis revealed a single class of high affinity IGF-IR binding sites with a similar dissociation constant (Kd: 0.32 +/- 0.1 nmol/l vs 0.22 +/- 0.08 nmol/l) for both normal adrenomedullary cells and pheochromocytomas. However, specific 125I-labeled IGF-I binding and the calculated receptor concentration were significantly elevated in pheochromocytomas as compared with normal adrenomedullary cells (58.3 +/- 5 vs 24.3 +/- 12 nmol/kg protein; P < 0.05). In summary, our results demonstrate significant overexpression of the IGF-IR in human pheochromocytomas. This suggests a possible role of the IGF system in the pathogenesis of adrenal neoplasia and thus IGF-IR may be a target for future therapeutic approaches.
Fottner
Christian
C
Schwerpunkt Endokrinologie und Stoffwechselerkrankungen, I Medizinische Klinik und Poliklinik der Johannes Gutenberg Universität Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany.
Minnemann
Timo
T
Kalmbach
Sarah
S
Weber
Matthias M
MM
D000313:Adrenal Medulla / Q000378:metabolism; D000328:Adult; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D010673:Pheochromocytoma / Q000235:genetics* / Q000378:metabolism*; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics; D017526:Receptor, IGF Type 1 / Q000235:genetics* / Q000378:metabolism*
D012333:RNA, Messenger; D017526:Receptor, IGF Type 1