Overexpression of Pax5 is not sufficient for neoplastic transformation of mouse neuroectoderm.
The developmental control genes of the Pax family are essential for brain development. Several Pax genes are also involved in chromosomal translocations causing malignancies in humans, and Pax5 expression is deregulated in medulloblastomas. We have investigated whether Pax5 can induce tumors in the developing mouse brain. Primary mouse embryonic neuroectodermal cells were retrovirally transduced with mouse Pax5 and transplanted into the brain of syngeneic host mice. No tumors developed in 36 transplants after one year, and there were no alterations in the differentiation pattern of the neural transplants. We then generated transgenic mice expressing human Pax5 under control of the Engrailed-2 promoter, which is expressed in the cerebellar external granule cell layer and in medulloblastomas. Sustained expression was achieved in the cerebellum of transgenic animals throughout lifetime. Expression levels were similar to those observed in human medulloblastomas. Again, cerebellar morphogenesis was undisturbed, and no tumors arose. These results strongly argue against a dominant transforming activity of PAX5 in NEC and in cerebellar granule cell precursors of mice, and underline the restricted tissue-specificity of PAX5 related oncogenesis.
Steinbach
J P
JP
Institute of Neuropathology, University Hospital, Zurich, Switzerland.
Kozmik
Z
Z
Pfeffer
P
P
Aguzzi
A
A
D016475:3T3 Cells; D000818:Animals; D001921:Brain / Q000166:cytology / Q000196:embryology*; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D017690:Cell Transplantation; D002531:Cerebellum / Q000378:metabolism / Q000502:physiology; D004268:DNA-Binding Proteins; D004475:Ectoderm / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D005136:Eye Proteins; D018507:Gene Expression Regulation, Developmental; D005822:Genetic Vectors / Q000235:genetics; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics; D051757:PAX5 Transcription Factor; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D011401:Promoter Regions, Genetic / Q000235:genetics; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D012097:Repressor Proteins; D012190:Retroviridae / Q000235:genetics; D014157:Transcription Factors; D014162:Transfection; D000099266:Engrailed 2 Protein
D004268:DNA-Binding Proteins; D005136:Eye Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D051757:PAX5 Transcription Factor; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D011506:Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D000099266:Engrailed 2 Protein; C497281:PAX5 protein, human; C000605730:PAX6 protein, human; C497282:Pax5 protein, mouse; C000605732:Pax6 protein, mouse