Haploinsufficiency of tumor suppressor pten predisposes to hemangiosarcoma in zebrafish
- Authors
- Choorapoikayil, S., Kuiper, R.V., de Bruin, A., and den Hertog, J.
- ID
- ZDB-PUB-111117-43
- 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.