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 language | English (US) |
|---|---|
| Pages (from-to) | 222-224 |
| Number of pages | 3 |
| Journal | Nature Genetics |
| Volume | 27 |
| Issue number | 2 |
| DOIs | |
| State | Published - 2001 |
| Externally published | Yes |
Fingerprint
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 journal › Article
}
TY - JOUR
T1 - Pten and p27KIP1 cooperate in prostate cancer tumor suppression in the mouse
AU - Di Cristofano, Antonio
AU - De Acetis, Marika
AU - Koff, Andrew
AU - Cordon-Cardo, Carlos
AU - P Pandolfi, Pier
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0034746302&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034746302&partnerID=8YFLogxK
U2 - 10.1038/84879
DO - 10.1038/84879
M3 - Article
C2 - 11175795
AN - SCOPUS:0034746302
VL - 27
SP - 222
EP - 224
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 2
ER -