Insulin-like growth factor-II expression is down-regulated in TrkA-transfected SK-N-AS neuroblastoma cells.
Expression level of trkA tyrosine kinase receptor for nerve growth factor is a major prognostic determinant of neuroblastoma, suggesting that defective trkA-mediated signaling is responsible for the tumorigenesis of this childhood malignancy. We investigated the biologic effect of trkA, with special reference to its effect on insulin-like growth factor-II (IGF-II) expression, in SK-N-AS human neuroblastoma cells transfected with human trkA cDNA. Nerve growth factor treatment of trkA-transfected cells promoted growth and changed the morphologic phenotype into a substrate-adherent, flatter phenotype (S-type), and down-regulated the mRNA expression of IGF-II. The effects on both growth and the morphologic differentiation of SK-N-AS cells differed significantly from those of previous studies, and implied that trkA effects can be diverse, depending on the phenotype of the individual neuroblastoma cells. Immunohistochemical screening of trkA and IGF-II expression in adrenal neuroblastomas (n = 25) also favored the nonoverlapping pattern of trkA and IGF-II expression (p < 0.05). Because IGF-II is believed to play a significant role in the tumorigenesis of neuroblastoma, the inverse relationship between trkA and IGF-II strongly suggests that a low level of trkA can be a feature of the pathogenetic mechanism of IGF-II expressing adrenal neuroblastomas.
Kim
C J
CJ
Department of Pathology, Seoul National University College of Medicine, Korea. cjkim@snu.ac.kr
Chi
J G
JG
Thiele
C J
CJ
D000310:Adrenal Gland Neoplasms / Q000378:metabolism; D002675:Child, Preschool; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007335:Insulin-Like Growth Factor II / Q000032:analysis / Q000235:genetics*; D008297:Male; D009414:Nerve Growth Factors / Q000494:pharmacology; D009447:Neuroblastoma / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D020917:Receptor, trkA; D017475:Receptors, Nerve Growth Factor / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D014162:Transfection
D009414:Nerve Growth Factors; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D017475:Receptors, Nerve Growth Factor; D007335:Insulin-Like Growth Factor II; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA