title: Establishment of a novel neuroblastoma mouse model.
abstract: Neuroblastoma is the most common childhood cancer, which arises from sympathetic neural precursors. Because the prognosis of advanced neuroblastoma is known to be poor, developments of new anti-cancer drugs are desperately needed. For screening of therapeutic drugs for neuroblastoma, genetically engineered animal models would be useful. In an attempt to obtain transgenic mice carrying simian virus 40 T-antigen gene under control of tetracycline responsive elements with cytomegalovirus promoter, we found one line of mice exhibiting bilateral adrenal tumors by leakage expression of T-antigen in adrenal gland. These adrenal tumors contained small round tumor cells with increased N/C ratio, showing chromogranin A and neuron specific enolase-like immunoreactivity. By electron microscopy, tumor cells containing neuritic processes with synaptic vesicles surrounding them were observed. The plasma levels of dopamine were significantly elevated in these transgenic mice. MYCN expression levels were significantly elevated in these tumors. These findings indicated that the adrenal tumor was a neuroblastoma. This mouse model would be a useful tool for development of chemotherapeutic drugs and understanding the etiology of neuroblastoma.
authors.affiliation: Ghrelin Research Project, Translational Research Center, Kyoto University Hospital, Sakyo-ku, Kyoto 606-8507, Japan. hiwaku@kuhp.kyoto-u.ac.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Iwakura
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ariyasu
authors.forename: Naotetsu
authors.initials: N
authors.lastname: Kanamoto
authors.forename: Kiminori
authors.initials: K
authors.lastname: Hosoda
authors.forename: Kazuwa
authors.initials: K
authors.lastname: Nakao
authors.forename: Kenji
authors.initials: K
authors.lastname: Kangawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Akamizu
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000375:Aging; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics; D053379:Chromogranin A / Q000378:metabolism; D003587:Cytomegalovirus / Q000235:genetics; D004298:Dopamine / Q000097:blood; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D009374:Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016501:Neurites / Q000473:pathology; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D011401:Promoter Regions, Genetic; D013572:Synaptic Vesicles / Q000473:pathology
chemical_list: D000952:Antigens, Polyomavirus Transforming; D053379:Chromogranin A; D010751:Phosphopyruvate Hydratase; D004298:Dopamine