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PMID:17704803

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Citation

Faucherre, A, Taylor, GS, Overvoorde, J, Dixon, JE and Hertog, J (2008) Zebrafish pten genes have overlapping and non-redundant functions in tumorigenesis and embryonic development. Oncogene 27:1079-86

Abstract

In human cancer, PTEN (Phosphatase and TENsin homolog on chromosome 10, also referred to as MMAC1 and TEP1) is a frequently mutated tumor suppressor gene. We have used the zebrafish as a model to investigate the role of Pten in embryonic development and tumorigenesis. The zebrafish genome encodes two pten genes, ptena and ptenb. Here, we report that both Pten gene products from zebrafish are functional. Target-selected inactivation of ptena and ptenb revealed that Ptena and Ptenb have redundant functions in embryonic development, in that ptena-/- and ptenb-/- mutants did not show embryonic phenotypes. Homozygous single mutants survived as adults and they were viable and fertile. Double homozygous ptena-/-ptenb-/- mutants died at 5 days post fertilization with pleiotropic defects. These defects were rescued by treatment with the phosphatidylinositol-3-kinase inhibitor, LY294002. Double homozygous embryos showed enhanced cellular proliferation. In addition, cell survival was dramatically enhanced in embryos that lack functional Pten upon gamma-irradiation. Surprisingly, adult ptenb-/- zebrafish developed ocular tumors later in life, despite the expression of ptena in adult eyes. We conclude that whereas Ptena and Ptenb have redundant functions in embryonic development, they apparently do not have completely overlapping functions later in life. These pten mutant zebrafish represent a unique model to screen for genetic and/or chemical suppressors of Pten loss-of-function.

Links

PubMed Online version:10.1038/sj.onc.1210730

Keywords

Adult; Animals; Animals, Genetically Modified; Eye Neoplasms/genetics; Female; Genes, Tumor Suppressor/physiology; Humans; Isoenzymes/genetics; Neoplasms/embryology; Neoplasms/genetics; PTEN Phosphohydrolase/genetics; PTEN Phosphohydrolase/physiology; Phosphoprotein Phosphatases/genetics; Phosphoprotein Phosphatases/physiology; Pregnancy; Zebrafish/embryology; Zebrafish/genetics; Zebrafish Proteins/genetics; Zebrafish Proteins/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

DANRE:A0A2R8PY11

enables

GO:0042577: lipid phosphatase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

DANRE:A0A2R8PY11

involved_in

GO:0046856: phosphatidylinositol dephosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DANRE:A0A2R8Q8H3

enables

GO:0042577: lipid phosphatase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

DANRE:A0A2R8Q8H3

involved_in

GO:0046856: phosphatidylinositol dephosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DANRE:A0A2R8RK27

enables

GO:0042577: lipid phosphatase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

DANRE:A0A2R8RK27

involved_in

GO:0046856: phosphatidylinositol dephosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DANRE:E7FC59

enables

GO:0042577: lipid phosphatase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

DANRE:E7FC59

involved_in

GO:0046856: phosphatidylinositol dephosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DANRE:F1Q5Y5

enables

GO:0042577: lipid phosphatase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

DANRE:F1Q5Y5

involved_in

GO:0046856: phosphatidylinositol dephosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DANRE:F6NM25

enables

GO:0042577: lipid phosphatase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

DANRE:F6NM25

involved_in

GO:0046856: phosphatidylinositol dephosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DANRE:Q561V0

enables

GO:0042577: lipid phosphatase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

DANRE:Q561V0

involved_in

GO:0046856: phosphatidylinositol dephosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DANRE:Q6PC66

enables

GO:0042577: lipid phosphatase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

DANRE:Q6PC66

involved_in

GO:0046856: phosphatidylinositol dephosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DANRE:Q6TGR5

enables

GO:0042577: lipid phosphatase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

DANRE:Q6TGR5

involved_in

GO:0046856: phosphatidylinositol dephosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DANRE:Q6TGR6

enables

GO:0042577: lipid phosphatase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

DANRE:Q6TGR6

involved_in

GO:0046856: phosphatidylinositol dephosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DANRE:Q6TGR7

enables

GO:0042577: lipid phosphatase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

DANRE:Q6TGR7

involved_in

GO:0046856: phosphatidylinositol dephosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DANRE:Q7ZZ56

enables

GO:0042577: lipid phosphatase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

DANRE:Q7ZZ56

involved_in

GO:0046856: phosphatidylinositol dephosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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