Activation of trkA induces differentiation and inhibits the growth of JK-GMS Askin tumor cells.
Peripheral primitive neuroectodermal tumor (PNET) and Ewing's sarcoma (ES) constitute a unique group of small round cell tumors in childhood and young adults that are characterized by the same chromosomal translocation t(11;22)(q24;q12). Recently, the expression of neurotrophin receptors has been found in various human tumors including PNET/ES, but the functional significance of these receptor expressions has not been documented in PNET/ES. In the present study, we investigated the biologic effects of trkA neurotrophin receptor activation by nerve growth factor (NGF) in a newly established Askin tumor cell line, JK-GMS, which constitutively expresses a high level of trkA. The activation of trkA induced differentiation and inhibited the growth of JK-GMS cells, which was characteristically associated with down-regulation of c-myc and N-myc mRNA expression. NGF did not exert significant changes in two different PNET/ES cell lines, CADO-ES1 and RD-ES, which did not express detectable levels of trkA. The biologic effects mediated by NGF were abrogated by treatment of the cells with K-252a, and the treatment with brain-derived neurotrophic factor did not affect the biologic behavior of JK-GMS cells, indicating that the effects are trkA specific. The results observed were quite similar to those of neuroblastoma cells, another childhood tumor of neural crest origin. Overall findings strongly suggest that the trkA-mediated signaling pathway plays a crucial role in controlling the basic biologic properties of JK-GMS cells.
Kim
Gi-Jin
GJ
Department of Pathology, Seoul National University College of Medicine, Seoul, Korea. cjkim@plaza.snu.ac.kr
Kim
Chong Jai
CJ
Cho
So Young
SY
Chung
In Pyung
IP
Park
Sun-Hwa
SH
Lee
Min Jung
MJ
Chi
Je G
JG
D000293:Adolescent; D001483:Base Sequence; D003994:Bucladesine / Q000494:pharmacology; D002454:Cell Differentiation; D002455:Cell Division; D017931:DNA Primers; D006801:Humans; D007621:Karyotyping; D008297:Male; D018242:Neuroectodermal Tumors, Primitive / Q000378:metabolism* / Q000473:pathology; D020917:Receptor, trkA / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D014212:Tretinoin; D003994:Bucladesine; D020917:Receptor, trkA