title: Haploinsufficiency of the genes encoding the tumor suppressor Pten predisposes zebrafish to hemangiosarcoma.
abstract: PTEN is an essential tumor suppressor that antagonizes Akt/PKB signaling. The zebrafish genome encodes two Pten genes, ptena and ptenb. Here, we report that zebrafish mutants that retain a single wild-type copy of ptena or ptenb (ptena(+/-)ptenb(-/-) or ptena(-/-)ptenb(+/-)) are viable and fertile. ptena(+/-)ptenb(-/-) fish develop tumors at a relatively high incidence (10.2%) and most tumors developed close to the eye (26/30). Histopathologically, the tumor masses were associated with the retrobulbar vascular network and diagnosed as hemangiosarcomas. A single tumor was identified in 42 ptena(-/-)ptenb(+/-) fish and was also diagnosed as hemangiosarcoma. Immunohistochemistry indicated that the tumor cells in ptena(+/-)ptenb(-/-) and ptena(-/-)ptenb(+/-) fish proliferated rapidly and were of endothelial origin. Akt/PKB signaling was activated in the tumors, whereas Ptena was still detected in tumor tissue from ptena(+/-)ptenb(-/-) zebrafish. We conclude that haploinsufficiency of the genes encoding Pten predisposes to hemangiosarcoma in zebrafish.
authors.affiliation: Hubrecht Institute-KNAW and University Medical Center, CT, Utrecht, The Netherlands.
authors.forename: Suma
authors.initials: S
authors.lastname: Choorapoikayil
authors.forename: Raoul V
authors.initials: RV
authors.lastname: Kuiper
authors.forename: Alain
authors.initials: A
authors.lastname: de Bruin
authors.forename: Jeroen
authors.initials: J
authors.lastname: den Hertog
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D004195:Disease Models, Animal; D055786:Gene Knockout Techniques; D016147:Genes, Tumor Suppressor; D020022:Genetic Predisposition to Disease; D057895:Haploinsufficiency; D006394:Hemangiosarcoma / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010749:Phosphoprotein Phosphatases / Q000172:deficiency / Q000235:genetics*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D015027:Zebrafish / Q000235:genetics*; D029961:Zebrafish Proteins / Q000172:deficiency / Q000235:genetics*
chemical_list: D029961:Zebrafish Proteins; D051057:Proto-Oncogene Proteins c-akt; D010749:Phosphoprotein Phosphatases; C511364:Ptena protein, zebrafish; C511365:Ptenb protein, zebrafish
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