trk and ret proto-oncogene expression in human neuroblastoma specimens: high frequency of trk expression in non-advanced stages.
Forty-three fresh tumor specimens of human neuroblastoma belonging to different clinical stages were analyzed for the expression of 2 proto-oncogenes: trk, which encodes a tyrosine-kinase receptor for nerve growth factor (NGF) and ret, another receptor-type tyrosine kinase whose ligand is unknown. The mRNA expression of the trk gene was detected in 67.4% of cases, with increased frequency in I, II and IVs Evans' stages and in patients with favorable prognosis according to the Shimada classification. Moreover, trk expression inversely correlated with Nmyc-gene amplification. ret mRNA was found in 36.8% of cases and equally distributed in the different stages. In addition, ngfR (low-affinity NGF receptor)-gene expression was present in 9 out of 25 cases. The simultaneous presence of mRNA related to both forms of the NGF receptor, while not proving the presence of a functional receptor, indicates the existence of a sub-set of neuroblastoma cells potentially responsive to NGF.
Division of Experimental Oncology A, Istituto Nazionale Tumori, Milan, Italy.
M G
MG
Borrello
I
I
Bongarzone
M A
MA
Pierotti
R
R
Luksch
M
M
Gasparini
P
P
Collini
S
S
Pilotti
M G
MG
Rizzetti
P
P
Mondellini
B
B
De Bernardi
D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D004273:DNA, Neoplasm / Q000032:analysis; D029721:Drosophila Proteins; D015870:Gene Expression / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000235:genetics; D009447:Neuroblastoma / Q000737:chemistry / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016133:Polymerase Chain Reaction / Q000379:methods; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000032:analysis* / Q000235:genetics; D051096:Proto-Oncogene Proteins c-ret; D011519:Proto-Oncogenes / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis*; D012334:RNA, Neoplasm / Q000032:analysis; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA; D016019:Survival Analysis; D014158:Transcription, Genetic
D004273:DNA, Neoplasm; D029721:Drosophila Proteins; C000715470:MAS1 protein, human; D009414:Nerve Growth Factors; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA; C416649:Ret protein, Drosophila