INSULIN-LIKE GROWTH-FACTOR-II MESSENGER-RNA, PEPTIDES, AND RECEPTORS IN A THORACOPULMONARY MALIGNANT SMALL ROUND-CELL TURNER

Insulin-like growth factor-(IGF) II and the IGF-I and IGF-II/mannose 6 -phosphate receptors were expressed in a thoracopulmonary malignant sm all 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 concentration s of 61 and 41 ng/g/tumor tissue, respectively. By a combined reverse transcription-polymerase chain reaction analysis, the authors also sho w that the MSRCT expresses IGF-I and IGF-II/mannose 6-phosphate recept or mRNA. The plasma concentration of IGF-II was 600 ng/ml and within t he 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 lev el of the 41.5, 38.5, and 30 kDa IGFBP were approximately 3-fold eleva ted. 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.