{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T22:19:34Z","timestamp":1790720374830,"version":"4.1.0"},"reference-count":46,"publisher":"Bioscientifica","issue":"2","content-domain":{"domain":["journals.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2007,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Hereditary medullary thyroid carcinoma (MTC) is caused by germline mutations in the RET proto-oncogene, resulting in constitutive activation of the RET tyrosine kinase. A substantial proportion of sporadic MTCs also have RET mutations, making the RET tyrosine kinase a potential therapeutic target in MTC. We have established a transplantable MTC in nude mice from a sporadic human MTC carrying a RET C634R mutation. Transplanted tumors had an exponential growth rate with an approximate doubling time of about 3 weeks, and expressed a neuroendocrine phenotype characteristic of MTC, e.g., expression of calcitonin, chromogranin A (CgA), synaptophysin, synaptic vesicle protein 2 (SV2), vesicular monoamine transporter-1 and -2, carcinoembryonic antigen, cytokeratin 8\/18, epithelial cadherin, and neural cell adhesion molecule. Plasma calcitonin and CgA levels were elevated in tumor-bearing mice and correlated with tumor size. Cytogenetic analysis, including spectral karyotyping, confirmed the human origin of the xenografted tumors and demonstrated an abnormal, near triploid karyotype. Treatment of tumor-bearing nude mice with the tyrosine kinase inhibitor ZD6474, which specifically inhibits RET, epidermal growth factor receptor (EGFR), and vascular endothelium growth factor receptor (VEGFR) tyrosine kinases, resulted in a dose-dependent inhibition of tumor growth. Oral ZD6474 given once daily (250 mg\/kg, 5 days\/week) reduced tumor volume to 11% when compared with controls after 4 weeks. Our results show that this transplantable MTC, designated GOT2, represents a novel and useful model for studies of MTC and RET tyrosine kinase-dependent tumor growth.<\/jats:p>","DOI":"10.1677\/erc-06-0033","type":"journal-article","created":{"date-parts":[[2007,7,17]],"date-time":"2007-07-17T11:22:00Z","timestamp":1184671320000},"page":"433-444","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-8","source":"Crossref","is-referenced-by-count":23,"title":["A transplantable human medullary thyroid carcinoma as a model for RET tyrosine kinase-driven tumorigenesis"],"prefix":"10.1530","volume":"14","author":[{"given":"Viktor","family":"Johanson","sequence":"first","affiliation":[{"name":"1Lundberg Laboratory for Cancer Research, Sahlgrenska University Hospital, SE-413 45 Go\u0308teborg, Sweden"},{"name":"2Department of Surgery, Sahlgrenska University Hospital, SE-413 45 Go\u0308teborg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ha\u030akan","family":"Ahlman","sequence":"additional","affiliation":[{"name":"1Lundberg Laboratory for Cancer Research, Sahlgrenska University Hospital, SE-413 45 Go\u0308teborg, Sweden"},{"name":"2Department of Surgery, Sahlgrenska University Hospital, SE-413 45 Go\u0308teborg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Bernhardt","sequence":"additional","affiliation":[{"name":"4Department of Radiation Physics, Sahlgrenska University Hospital, SE-413 45 Go\u0308teborg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svante","family":"Jansson","sequence":"additional","affiliation":[{"name":"1Lundberg Laboratory for Cancer Research, Sahlgrenska University Hospital, SE-413 45 Go\u0308teborg, Sweden"},{"name":"2Department of Surgery, Sahlgrenska University Hospital, SE-413 45 Go\u0308teborg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Ko\u0308lby","sequence":"additional","affiliation":[{"name":"1Lundberg Laboratory for Cancer Research, Sahlgrenska University Hospital, SE-413 45 Go\u0308teborg, Sweden"},{"name":"2Department of Surgery, Sahlgrenska University Hospital, SE-413 45 Go\u0308teborg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fredrik","family":"Persson","sequence":"additional","affiliation":[{"name":"1Lundberg Laboratory for Cancer Research, Sahlgrenska University Hospital, SE-413 45 Go\u0308teborg, Sweden"},{"name":"3Department of Pathology, Sahlgrenska University Hospital, SE-413 45 Go\u0308teborg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Go\u0308ran","family":"Stenman","sequence":"additional","affiliation":[{"name":"1Lundberg Laboratory for Cancer Research, Sahlgrenska University Hospital, SE-413 45 Go\u0308teborg, Sweden"},{"name":"3Department of Pathology, Sahlgrenska University Hospital, SE-413 45 Go\u0308teborg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Swa\u0308rd","sequence":"additional","affiliation":[{"name":"1Lundberg Laboratory for Cancer Research, Sahlgrenska University Hospital, SE-413 45 Go\u0308teborg, Sweden"},{"name":"2Department of Surgery, Sahlgrenska University Hospital, SE-413 45 Go\u0308teborg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Wa\u0308ngberg","sequence":"additional","affiliation":[{"name":"1Lundberg Laboratory for Cancer Research, Sahlgrenska University Hospital, SE-413 45 Go\u0308teborg, Sweden"},{"name":"2Department of Surgery, Sahlgrenska University Hospital, SE-413 45 Go\u0308teborg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mats","family":"Stridsberg","sequence":"additional","affiliation":[{"name":"5Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ola","family":"Nilsson","sequence":"additional","affiliation":[{"name":"1Lundberg Laboratory for Cancer Research, Sahlgrenska University Hospital, SE-413 45 Go\u0308teborg, Sweden"},{"name":"3Department of Pathology, Sahlgrenska University Hospital, SE-413 45 Go\u0308teborg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"2026070906054458700_BRAUCKHOFF-ETAL-2004","doi-asserted-by":"crossref","unstructured":"Brauckhoff\n            M\n          , Lorenz K, Ukkat J, Brauckhoff K, Gimm O & Dralle H \n2004 Medullary thyroid carcinoma. \nScandinavian Journal of Surgery93249\u2013260.","DOI":"10.1177\/145749690409300402"},{"key":"2026070906054458700_CARLOMAGNO-ETAL-2002A","unstructured":"Carlomagno\n            F\n          , Vitagliano D, Guida T, Napolitano M, Vecchio G, Fusco A, Gazit A, Levitzki A & Santoro M \n2002a The kinase inhibitor PP1 blocks tumorigenesis 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