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Haploinsufficiency of the genes encoding the tumor suppressor Pten predisposes zebrafish to hemangiosarcoma
Suma Choorapoikayil, Raoul V. Kuiper, Alain de Bruin, Jeroen den Hertog


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.



    The authors declare that they do not have any competing or financial interests.


    S.C. and J.d.H. conceived the experiments; S.C., R.V.K., A.d.B. and J.d.H. designed the experiments; S.C. and R.V.K. performed the experiments; S.C., R.V.K., A.d.B. and J.d.H. analyzed the data and wrote the manuscript.


    This work was supported in part by an EU (FP7) grant [HEALTH-F2-2008-201439 (ZF-CANCER)].


    Supplementary material for this article is available at

  • Received June 8, 2011.
  • Accepted November 3, 2011.

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