The expression profile of alternatively spliced neuronal c-src RNA distinguishes between human tumours of the sympatho-adrenal lineage.
Human neuronal and neuroendocrine tumour specimens and cell lines were analysed regarding proteins and transcripts coded by the proto-oncogene c-src. At the protein level, most of the neuroblastomas and phaeochromocytomas expressed the neuronal c-src form, pp60c-srcN. None of the other neuroendocrine tumours, i.e. paragangliomas, neuroendocrine pancreatic tumours, or carcinoid tumours and small-cell lung carcinomas of different types, appeared to express the neuronal form. In the brain, c-src is transcribed into 3 differently spliced mRNA variants, c-src, c-srcNI, and c-srcNI+NII. The expression of these transcripts was analysed by PCR amplification of fragments covering the mini-exons I and NII of the corresponding cDNAs. The PCR products were analysed by Southern hybridization and characterized by determination of their sequences. Neuroblastomas, paragangliomas, retinoblastomas and the phaeochromocytomas expressed neuronal c-src splice variants. However, whereas neuroblastomas and retinoblastomas contained all 3 transcripts, the phaeochromocytomas and paragangliomas expressed, with 2 exceptions, only the c-src and the c-srcNI+NII mRNA species. To assess whether neuroblastomas display adrenal chromaffin characteristics, they were analysed regarding expression of the chromaffin marker enzyme, phenylethanolamine-N-methyl transferase. Whereas phaeochromocytomas were positive, all neuroblastomas were immuno-chemically negative for this enzyme. These results and the c-src expression profile suggest that neuroblastomas, including those with an adrenal location, do not originate from the adrenal chromaffin differentiation lineage. The data further suggest neuronal c-srcNI mRNA as a marker for sympathetic neuronal cells of the sympatho-adrenal lineage.
Ortoft
E
E
Department of Pathology, University of Uppsala, Sweden.
Bjelfman
C
C
Hedborg
F
F
Grimelius
L
L
Påhlman
S
S
D000310:Adrenal Gland Neoplasms / Q000235:genetics* / Q000473:pathology*; D001483:Base Sequence; D015139:Blotting, Southern; D002454:Cell Differentiation / Q000502:physiology; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics; D005091:Exons; D015870:Gene Expression; D016391:Genes, src; D014644:Genetic Variation; D006801:Humans; D008969:Molecular Sequence Data; D009423:Nervous System Neoplasms / Q000235:genetics* / Q000473:pathology*; D009447:Neuroblastoma / Q000235:genetics / Q000473:pathology; D018358:Neuroendocrine Tumors / Q000235:genetics* / Q000473:pathology*; D015688:Oncogene Protein pp60(v-src) / Q000032:analysis; D010235:Paraganglioma / Q000235:genetics / Q000473:pathology; D010625:Phenylethanolamine N-Methyltransferase / Q000235:genetics; D010673:Pheochromocytoma / Q000235:genetics / Q000473:pathology; D016133:Polymerase Chain Reaction; D000090063:Proto-Oncogene Mas; D012326:RNA Splicing; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics*; D012334:RNA, Neoplasm / Q000032:analysis / Q000235:genetics*; D012194:RNA-Directed DNA Polymerase; D012175:Retinoblastoma / Q000235:genetics / Q000473:pathology; D013564:Sympathetic Nervous System / Q000473:pathology; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D010625:Phenylethanolamine N-Methyltransferase; D015688:Oncogene Protein pp60(v-src); D012194:RNA-Directed DNA Polymerase