Establishment of a novel neuroblastoma mouse model

• Published in: International journal of oncology Vol. 33; no. 6; pp. 1195 - 1199
• Main Authors: IWAKURA, Hiroshi, ARIYASU, Hiroyuki, KANAMOTO, Naotetsu, HOSODA, Kiminori, NAKAO, Kazuwa, KANGAWA, Kenji, AKAMIZU, Takashi
• Format: Journal Article
• Language: English
• Published: Athens Editorial Academy of the International Journal of Oncology 01.12.2008
• Subjects: Adrenal Gland Neoplasms - genetics; Adrenal Gland Neoplasms - metabolism; Adrenal Gland Neoplasms - pathology; Aging; Animals; Antigens, Polyomavirus Transforming - genetics; Biological and medical sciences; Chromogranin A - metabolism; Cytomegalovirus; Cytomegalovirus - genetics; Dopamine - blood; Gene Expression Regulation, Neoplastic; Genes, myc; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Inbred ICR; Mice, Transgenic; Neoplasms, Experimental - genetics; Neoplasms, Experimental - metabolism; Neoplasms, Experimental - pathology; Neurites - pathology; Neuroblastoma - genetics; Neuroblastoma - metabolism; Neuroblastoma - pathology; Neurology; Phosphopyruvate Hydratase - metabolism; Promoter Regions, Genetic; Simian virus 40; Synaptic Vesicles - pathology; Tumors; Tumors of the nervous system. Phacomatoses; Animal model; Nervous system diseases; Polyomavirus; Rodentia; Papovaviridae; Malignant tumor; Neuroblastoma; Simian virus 40; Virus; Vertebrata; Mammalia; Cancerology; Mouse; Autonomic neuropathy; transgenic models; Cancer
• ISSN: 1019-6439
• DOI: 10.3892/ijo_00000109

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.