ZFIN ID: ZDB-PUB-111117-43
Haploinsufficiency of tumor suppressor pten predisposes to hemangiosarcoma in zebrafish
Choorapoikayil, S., Kuiper, R.V., de Bruin, A., and den Hertog, J.
Date: 2012
Source: Disease models & mechanisms   5(2): 241-247 (Journal)
Registered Authors: den Hertog, Jeroen
Keywords: none
MeSH Terms:
  • Animals
  • Cell Proliferation
  • Disease Models, Animal
  • Gene Knockout Techniques
  • Genes, Tumor Suppressor*
  • Genetic Predisposition to Disease
  • Haploinsufficiency
  • Hemangiosarcoma/etiology*
  • Hemangiosarcoma/genetics
  • Hemangiosarcoma/metabolism
  • Hemangiosarcoma/pathology
  • Phosphoprotein Phosphatases/deficiency
  • Phosphoprotein Phosphatases/genetics*
  • Proto-Oncogene Proteins c-akt/metabolism
  • Signal Transduction
  • Zebrafish/genetics*
  • Zebrafish Proteins/deficiency
  • Zebrafish Proteins/genetics*
PubMed: 22071262 Full text @ Dis. Model. Mech.

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 pten, 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 that 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 pten predisposes to hemangiosarcoma in zebrafish.