Haploinsufficiency of the genes encoding the tumor suppressor Pten predisposes zebrafish to hemangiosarcoma | Zendy

Suma Choorapoikayil | Zendy; Raoul Kuiper | Zendy; Alain de Bruin | Zendy; Jeroen den Hertog | Zendy

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Haploinsufficiency of the genes encoding the tumor suppressor Pten predisposes zebrafish to hemangiosarcoma

Author(s) -

Suma Choorapoikayil,

Raoul Kuiper,

Alain de Bruin,

Jeroen den Hertog

Publication year - 2011

Publication title -

disease models and mechanisms

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.327

H-Index - 83

eISSN - 1754-8411

pISSN - 1754-8403

DOI - 10.1242/dmm.008326

Subject(s) - pten , zebrafish , haploinsufficiency , biology , cancer research , hemangiosarcoma , tumor suppressor gene , suppressor , protein kinase b , pi3k/akt/mtor pathway , oncogene , carcinogenesis , gene , pathology , microbiology and biotechnology , genetics , signal transduction , medicine , phenotype , cell cycle , angiosarcoma

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.

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