Insulin-like growth factor II mRNA, peptides, and receptors in a thoracopulmonary malignant small round cell tumor.
Insulin-like growth factor-(IGF) II and IGF-I and IGF-II/mannose 6-phosphate receptors were expressed in a thoracopulmonary malignant small round cell tumor (MSRCT) from a 14-year-old boy. Northern analysis showed that the MSRCT expresses multiple IGF-II mRNA of 6.0, 4.8, 4.2, and 2.2 kilobase from promoters P3 and P4 of the human IGF-II gene. Chromatography and radioimmunoassay revealed two forms of IGF-II with molecular masses of 7.5 kilodalton (kDa) and 10 kDa, corresponding to mature IGF-II and IGF-II with a C-terminal extension, in concentrations of 61 and 41 ng/g/tumor tissue, respectively. By a combined reverse transcription-polymerase chain reaction analysis, the authors also show that the MSRCT expresses IGF-I and IGF-II/mannose 6-phosphate receptor mRNA. The plasma concentration of IGF-II was 600 ng/ml and within the normal range of serum IGF-II. IGF binding proteins (IGFBP) of 41.5, 38.5, 34, 30, and 24 kDa were present in serum. Compared with normal plasma from healthy subjects and an age-matched group of boys, the level of the 41.5, 38.5, and 30 kDa IGFBP were approximately 3-fold elevated. The authors conclude that transcription of the IGF-II gene leads to the production of significant amounts of 10 kDa IGF-II and 7.5 kDa IGF-II. IGF-II may stimulate the proliferation of MSRCT by interaction with IGF-I receptors on the cells.
Nielsen
F C
FC
Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark.
Orskov
C
C
Haselbacher
G
G
Ramlau
J
J
Christiansen
J
J
Schmiegelow
K
K
Rehfeld
J F
JF
D000293:Adolescent; D015152:Blotting, Northern; D018288:Carcinoma, Small Cell / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis / Q000302:isolation & purification; D007335:Insulin-Like Growth Factor II / Q000096:biosynthesis* / Q000302:isolation & purification; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis*; D017526:Receptor, IGF Type 1 / Q000032:analysis; D017527:Receptor, IGF Type 2 / Q000032:analysis; D013899:Thoracic Neoplasms / Q000378:metabolism* / Q000473:pathology
D012333:RNA, Messenger; D012334:RNA, Neoplasm; D017527:Receptor, IGF Type 2; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D017526:Receptor, IGF Type 1