Defective expression of prohormone convertase 4 and enhanced expression of insulin-like growth factor II by pleural solitary fibrous tumor causing hypoglycemia.
A 75-year-old man was admitted to our hospital because of unconsciousness. His plasma glucose was very low, but his serum levels of insulin and IGF-I were also low. He was found to have a giant solitary pleural tumor, which was completely resected, after which his hypoglycemia ameliorated postoperatively. Histologically, the tumor was consistent with the pathological diagnosis of a solitary fibrous tumor derived from the pleura. Immunohistochemical study revealed positive immunostaining for IGF-II in tumor cells. The presence of high molecular weight (HMW) form of IGF-II in the tumor tissue and patient's serum was confirmed by Western blot analysis. Steady-state mRNA levels of IGF-II and prohormone convertases (PC) 4, a potential protease responsible for IGF-II processing, as determined by RT-PCR were about 14-fold greater and 5-fold less in the tumor tissue than those in normal placental tissue, respectively. Therefore, it is suggested that biologically active, unprocessed HMW form of IGF-II generated from the impaired processing of IGF-II precursor by the defective PC4 expression in the tumor was responsible for the non-islet cell tumor hypoglycemia (NICTH) in the present case.
Department of Clinical and Molecular Endocrinology, Tokyo Medical and Dental University Graduate School, Japan.
Yuji
Y
Tani
Toru
T
Tateno
Hajime
H
Izumiyama
Masaru
M
Doi
Takanobu
T
Yoshimoto
Yukio
Y
Hirata
D000368:Aged; D015153:Blotting, Western; D015870:Gene Expression; D006801:Humans; D007003:Hypoglycemia / Q000209:etiology*; D007150:Immunohistochemistry; D007328:Insulin / Q000097:blood; D007335:Insulin-Like Growth Factor II / Q000032:analysis* / Q000737:chemistry / Q000235:genetics; D008297:Male; D008970:Molecular Weight; D043484:Proprotein Convertases / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D054363:Solitary Fibrous Tumor, Pleural / Q000150:complications* / Q000201:enzymology* / Q000601:surgery; D013381:Subtilisins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism
D007328:Insulin; D011498:Protein Precursors; D012333:RNA, Messenger; D007335:Insulin-Like Growth Factor II; C489716:PCSK4 protein, human; D043484:Proprotein Convertases; D013381:Subtilisins