Reference SummaryDi Cristofano A, Nat Genet 2001 Feb;27(2):222-4
Title |
Pten and p27KIP1 cooperate in prostate cancer tumor suppression in the mouse. |
Authors |
Di Cristofano A; De Acetis M; Koff A; Cordon-Cardo C; Pandolfi PP |
Journal |
Nat Genet |
Volume |
27 |
Issue |
2 |
Year |
2001 |
Pages |
222-4 |
Abstract |
The genetic bases underlying prostate tumorigenesis are poorly understood. Inactivation of the tumor-suppressor gene PTEN and lack of p27(KIP1) expression have been detected in most advanced prostate cancers. But mice deficient for Cdkn1b (encoding p27(Kip1)) do not develop prostate cancer. PTEN activity leads to the induction of p27(KIP1) expression, which in turn can negatively regulate the transition through the cell cycle. Thus, the inactivation of p27(KIP1) 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 p27(Kip1) through the control of cell-cycle progression. |
Links |
J:67499 – MGI References 11175795 – National Library of Medicine/PubMed |
| Strain | Model Name | Treatment Agent(s) | Organ Affected | Frequency | Model Details |
|---|---|---|---|---|---|
| B6;129S1-Ptentm1Ppp/+ | Adrenal gland - Medulla tumor | Adrenal gland - Medulla |
0 - 100 |
||
| B6;129S1-Cdkn1btm1Ako Ptentm1Ppp/+ | Adrenal gland - Medulla tumor | Adrenal gland - Medulla |
100 |
||
| B6;129S1-Ptentm1Ppp/+ | Intestine - Large Intestine adenocarcinoma | Intestine - Large Intestine |
11 |
||
| B6;129S1-Cdkn1btm1Ako Ptentm1Ppp/+ | Intestine - Large Intestine adenocarcinoma | Intestine - Large Intestine |
16 |
||
| B6;129S1-Cdkn1btm1Ako Ptentm1Ppp/+ | Intestine - Small Intestine - Ileum polyp | Intestine - Small Intestine - Ileum |
100 |
||
| B6;129S1-Ptentm1Ppp/+ | Intestine - Small Intestine adenocarcinoma | Intestine - Small Intestine |
23 |
||
| B6;129S1-Cdkn1btm1Ako Ptentm1Ppp/+ | Intestine - Small Intestine adenocarcinoma | Intestine - Small Intestine |
52 |
||
| B6;129S1-Ptentm1Ppp/+ | Lung adenocarcinoma | Lung |
5.7 |
||
| B6;129S1-Cdkn1btm1Ako Ptentm1Ppp/+ | Lung adenocarcinoma | Lung |
0 |
||
| B6;129S1-Cdkn1btm1Ako Ptentm1Ppp/+ | Prostate gland carcinoma | Prostate gland |
25 |
||
| B6;129S1-Ptentm1Ppp/+ | Prostate gland prostatic intraepithelial neoplasia (PIN) | Prostate gland |
0 - 50 |
||
| B6;129S1-Cdkn1btm1Ako Ptentm1Ppp/+ | Prostate gland prostatic intraepithelial neoplasia (PIN) | Prostate gland |
100 |
||
| B6;129S1-Ptentm1Ppp/+ | Thyroid gland carcinoma - follicular | Thyroid gland |
0 - 58 |
||
| B6;129S1-Cdkn1btm1Ako Ptentm1Ppp/+ | Thyroid gland carcinoma - follicular | Thyroid gland |
100 |
||
| B6;129S1-Ptentm1Ppp/+ | Uterus - Endometrium hyperplasia | Uterus - Endometrium |
69 |
||
| B6;129S1-Cdkn1btm1Ako Ptentm1Ppp/+ | Uterus - Endometrium hyperplasia | Uterus - Endometrium |
100 |
||
| B6;129S1 | (Unspecified organ) tumor | (Unspecified organ) |
0 |
||
| C57BL/6-Cdkn1btm1Ako | (Unspecified organ) tumor | (Unspecified organ) |
0 |