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 center dot 8-fold higher mean IGF-IR mRNA levels than normal adrenomedullary cells (2-8 +/- 0-5x10(5) molecules/mu g RNA vs 7-8 +/- 1-2x10(5) molecules/mu g 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 (K-d: 0.32 +/- 0.1 nmol/l vs 0.22 +/- 0.08 nmol/l) for both normal adrenomedullary cells and pheochromocytomas. However, specific (125)l-labeled lGF-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.