Neuronal src and trk a protooncogene expression in neuroblastomas and patient prognosis.
Neuroblastomas present a wide variety of clinical and biological behaviors, which are reflected by the heterogeneous expressions of protooncogenes related to the neuronal differentiation and amplification of the N-myc gene. High expression of trk A and Ha-ras in neuroblastomas has been shown to be associated with an excellent patient outcome. We have previously reported that neuron-specific src mRNA was increased in chemically differentiated neuroblastoma cell lines and in clinically observed neuroblastomas without N-myc amplification. In the present study, to clarify both the value of neuronal c-srcN2 expression as a prognostic indicator and the significance of the coexpression of these protooncogenes, we examined the expression of 3 alternatively spliced src, trk A and Ha-ras in neuroblastoma tissues from 60 patients by competitive RNA-polymerase chain reaction (PCR). The results indicate that protooncogene expression in neuroblastomas correlated with a favorable outcome for c-srcN2 and trk A. N-myc gene was amplified exclusively in tumors with low levels of trk A. Low expression of c-srcN2 and trk A might thus characterize different aggressive phenotypes due to different signal transduction pathways of neural differentiation in neuroblastoma. The combined analyses for c-srcN2 and trk A expression by RNA-PCR should provide information about the biological phenotype of a neuroblastoma within a short period of time after obtaining tumor material.
Matsunaga
T
T
Department of Pediatric Surgery, Chiba University, School of Medicine, Japan.
Shirasawa
H
H
Enomoto
H
H
Yoshida
H
H
Iwai
J
J
Tanabe
M
M
Kawamura
K
K
Etoh
T
T
Ohnuma
N
N
D016259:Genes, myc; D011905:Genes, ras; D006801:Humans; D007223:Infant; D009362:Neoplasm Metastasis; D009447:Neuroblastoma / Q000378:metabolism*; D015513:Oncogene Proteins / Q000378:metabolism*; D016133:Polymerase Chain Reaction / Q000379:methods; D011379:Prognosis; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism*
D015513:Oncogene Proteins; C065400:oncogene protein trk; D016392:Proto-Oncogene Proteins pp60(c-src)