Pten and p27KIP1 cooperate in prostate cancer tumor suppression in the mouse Journal Article
| Authors: | Di Cristofano, A.; De Acetis, M.; Koff, A.; Cordon-Cardo, C.; P Pandolfi, P. |
| Article Title: | Pten and p27KIP1 cooperate in prostate cancer tumor suppression in the mouse |
| 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. |
| Keywords: | adolescent; genetics; nonhuman; cell proliferation; cell cycle protein; mouse; animal; mouse mutant; animals; cell cycle proteins; mice; animal tissue; cell cycle; phosphatase; animal experiment; animal model; mice, mutant strains; carcinogenesis; animalia; prostate cancer; prostatic neoplasms; gene expression regulation; cancer inhibition; tumor suppressor gene; cyclin dependent kinase inhibitor 1b; prostate tumor; protein p27; cyclin-dependent kinase inhibitor p27; tumor suppressor proteins; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; pten phosphohydrolase; gene inactivation; tumor suppressor protein; phosphoric monoester hydrolases; genes, tumor suppressor; cdkn1b protein, mouse; microtubule-associated proteins; microtubule associated protein; male; priority journal; article |
| Journal Title: | Nature Genetics |
| Volume: | 27 |
| Issue: | 2 |
| ISSN: | 1061-4036 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2001-02-01 |
| Start Page: | 222 |
| End Page: | 224 |
| Language: | English |
| DOI: | 10.1038/84879 |
| PUBMED: | 11175795 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 21 May 2015 -- Source: Scopus |
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