TY - JOUR
T1 - Activation of trkA induces differentiation and inhibits the growth of JK-GMS askin tumor cells
AU - Kim, Gi Jin
AU - Kim, Chong Jai
AU - Cho, So Young
AU - Chung, In Pyung
AU - Park, Sun Hwa
AU - Lee, Min Jung
AU - Chi, Je G.
N1 - Funding Information:
This research was supported in part by Grant 04-1999-0720 from the Seoul National University Hospital Research Fund and in part by Grant KOHTERF-99-12 of the Korean Human Technology Research Foundation. Address reprint requests to: Dr. Chong Jai Kim, Department of Pathology, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul, 110-799, Korea. E-mail: cjkim@plaza.snu.ac.kr
PY - 2002/2
Y1 - 2002/2
N2 - 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.
AB - 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.
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U2 - 10.1038/labinvest.3780414
DO - 10.1038/labinvest.3780414
M3 - Article
C2 - 11850535
AN - SCOPUS:0036173910
VL - 82
SP - 221
EP - 229
JO - Laboratory Investigation
JF - Laboratory Investigation
SN - 0023-6837
IS - 2
ER -