Pten and p27KIP1 cooperate in prostate cancer tumor suppression in the mouse

Antonio Di Cristofano, Marika De Acetis, Andrew Koff, Carlos Cordon-Cardo, Pier P Pandolfi

Research output: Contribution to journalArticle

373 Citations (Scopus)

Abstract

The genetic bases underlying prostate tumorigenesis are poorly understood. Inactivation of the tumor-suppressor gene PTEN and lack of p27KIP1 expression have been detected in most advanced prostate cancers1,2. But mice deficient for Cdkn1b (encoding p27Kip1) do not develop prostate cancer3-5. PTEN activity leads to the induction of P27KIP1 expression, which in turn can negatively regulate the transition through the cell cycle6. Thus, the inactivation of P27KIP1 may be epistatic to PTEN in the control of the cell cycle. Here we show that the concomitant inactivation of one Pten allele and one or both Cdkn1b alleles accelerates spontaneous neoplastic transformation and incidence of tumors of various histological origins. Cell proliferation, but not cell survival, is increased in Pten+/-/Cdkn1b-/- mice. Moreover, Pten+/-/Cdkn1b-/- mice develop prostate carcinoma at complete penetrance within three months from birth. These cancers recapitulate the natural history and pathological features of human prostate cancer. Our findings reveal the crucial relevance of the combined tumor-suppressive activity of Pten and p27Kip1 through the control of cell-cycle progression.

Original languageEnglish (US)
Pages (from-to)222-224
Number of pages3
JournalNature Genetics
Volume27
Issue number2
DOIs
StatePublished - 2001
Externally publishedYes

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Prostate
Prostatic Neoplasms
Cell Cycle Checkpoints
Neoplasms
Alleles
Penetrance
Tumor Suppressor Genes
Natural History
Cell Survival
Carcinogenesis
Cell Proliferation
Parturition
Carcinoma
Incidence

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Pten and p27KIP1 cooperate in prostate cancer tumor suppression in the mouse. / Di Cristofano, Antonio; De Acetis, Marika; Koff, Andrew; Cordon-Cardo, Carlos; P Pandolfi, Pier.

In: Nature Genetics, Vol. 27, No. 2, 2001, p. 222-224.

Research output: Contribution to journalArticle

Di Cristofano, A, De Acetis, M, Koff, A, Cordon-Cardo, C & P Pandolfi, P 2001, 'Pten and p27KIP1 cooperate in prostate cancer tumor suppression in the mouse', Nature Genetics, vol. 27, no. 2, pp. 222-224. https://doi.org/10.1038/84879
Di Cristofano, Antonio ; De Acetis, Marika ; Koff, Andrew ; Cordon-Cardo, Carlos ; P Pandolfi, Pier. / Pten and p27KIP1 cooperate in prostate cancer tumor suppression in the mouse. In: Nature Genetics. 2001 ; Vol. 27, No. 2. pp. 222-224.
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