Pten is essential for embryonic development and tumour suppression

Antonio Di Cristofano, Barbara Pesce, Carlos Cordon-Cardo, Pier Paolo Pandolfi

Research output: Contribution to journalArticle

1189 Citations (Scopus)

Abstract

The PTEN gene encodes a dual-specificity phosphatase mutated in a variety of human cancers. PTEN germline mutations are found in three related human autosomal dominant disorders, Cowden disease (CD), Lhermitte-Duclos disease (LDD) and Bannayan-Zonana syndrome (BZS), characterized by tumour susceptibility and developmental defects. To examine the role of PTEN in ontogenesis and tumour suppression, we disrupted mouse Pten by homologous recombination. Pten inactivation resulted in early embryonic lethality. Pten(-/-) ES cells formed aberrant embryoid bodies and displayed an altered ability to differentiate into endodermal, ectodermal and mesodermal derivatives. Pten(+/-) mice and chimaeric mice derived from Pten(+/-) ES cells showed hyperplastic-dysplastic changes in the prostate, skin and colon, which are characteristic of CD, LDD and BZS. They also spontaneously developed germ cell, gonadostromal, thyroid and colon tumours. In addition, Pten inactivation enhanced the ability of ES cells to generate tumours in nude and syngeneic mice, due to increased anchorage-independent growth and aberrant differentiation. These results support the notion that PTEN haploinsufficiency plays a causal role in CD, LDD and BZS pathogenesis, and demonstrate that Pten is a tumour suppressor essential for embryonic development.

Original languageEnglish (US)
Pages (from-to)348-355
Number of pages8
JournalNature Genetics
Volume19
Issue number4
DOIs
StatePublished - 1998
Externally publishedYes

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Multiple Hamartoma Syndrome
Embryonic Development
Neoplasms
Colon
Dual-Specificity Phosphatases
Embryoid Bodies
Haploinsufficiency
Germ-Line Mutation
Homologous Recombination
Nude Mice
Germ Cells
Prostate
Thyroid Gland

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Pten is essential for embryonic development and tumour suppression. / Di Cristofano, Antonio; Pesce, Barbara; Cordon-Cardo, Carlos; Pandolfi, Pier Paolo.

In: Nature Genetics, Vol. 19, No. 4, 1998, p. 348-355.

Research output: Contribution to journalArticle

Di Cristofano, A, Pesce, B, Cordon-Cardo, C & Pandolfi, PP 1998, 'Pten is essential for embryonic development and tumour suppression', Nature Genetics, vol. 19, no. 4, pp. 348-355. https://doi.org/10.1038/1235
Di Cristofano, Antonio ; Pesce, Barbara ; Cordon-Cardo, Carlos ; Pandolfi, Pier Paolo. / Pten is essential for embryonic development and tumour suppression. In: Nature Genetics. 1998 ; Vol. 19, No. 4. pp. 348-355.
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