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. 2001 Nov 15;15(22):2934-9.
doi: 10.1101/gad.929901.

Dmp1 is haplo-insufficient for tumor suppression and modifies the frequencies of Arf and p53 mutations in Myc-induced lymphomas

K Inoue  1 , F Zindy, D H Randle, J E Rehg, C J Sherr
Affiliations

VSports在线直播 - Dmp1 is haplo-insufficient for tumor suppression and modifies the frequencies of Arf and p53 mutations in Myc-induced lymphomas

K Inoue et al. Genes Dev. .

Abstract

Loss of Dmp1, an Arf transcriptional activator, leads to spontaneous tumorigenesis in mice, causing death from various forms of cancer by two years of age. Retention and expression of the wild-type Dmp1 allele in tumors arising in Dmp1(+/-) mice demonstrate that Dmp1 can be haplo-insufficient for tumor suppression. The mean latency of E(mu)-Myc-induced B-cell lymphomas is halved on a Dmp1(-/-) or Dmp1(+/-) genetic background. Although p53 mutations or Arf deletion normally occur in approximately 50% of E(mu)-Myc-induced lymphomas, Dmp1 loss obviates selection for such mutations, indicating that Dmp1 is a potent genetic modifier of the Arf-p53 pathway in vivo. VSports手机版.

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Figure 1
Figure 1
Tumor-free survival in cohorts of untreated Dmp1+/+, Dmp1+/−, and Dmp1−/− mice (left) and in animals neonatally exposed to DMBA (middle) or X rays (right). The numbers of animals in each group is indicated by the corresponding survival curve.
Figure 2
Figure 2
Retention and expression of the wild-type Dmp1 gene in T-cell lymphomas (A) and pulmonary adenocarcinomas (B) arising in Dmp1 heterozygotes. Tumors are designated by K numbers above the lanes. (B) (Lanes 1–5) Results with tumors obtained from untreated animals; (lanes 6–10) DMBA-treated animals. Protein was detected by direct immunoblotting of tumor cell lysates, and RNA by RT–PCR (not done for tumors K1310 and K3001 in B). Actin was used as a control for both procedures to guarantee equal loading. Results with normal tissues of the indicated genotypes appear in the right three lanes of each panel.
Figure 3
Figure 3
Tumor free survival (A) and Dmp1 status (B) of Eμ-Myc transgenic animals of the indicated Dmp1 genotypes. Dmp1 RNA and protein were detected by RT–PCR and immunoblotting, respectively, using actin as a control for loading.
Figure 4
Figure 4
Detection of Dmp1 RNA by in situ hybridization. Liver cells from Dmp1+/+ mice (A), stained with hematoxylin (blue) express Dmp1 RNA (E). Malignant lymphoma cells in Eμ-Myc transgenic mice, visualized by antibody staining for B220 antigen (brown), surrounded central veins and invaded adjacent liver sinusoids (B–D). Regions containing metastatic B-cells in livers from both Eμ-Myc Dmp1+/+ (B) and Eμ-Myc Dmp1+/− (C) mice revealed increased hybridization signals with a Dmp1 antisense probe (F,G), respectively, relative to that in normal liver (E), consistent with continued Dmp1 expression in lymphomas from heterozygous mice. Similar results were obtained in three of three Dmp1+/− animals. Background hybridization with tissues from Eμ-Myc Dmp1−/− mice (H) was equivalent to that obtained with a control Dmp1 sense probe (data not shown).
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References

    1. Adams JM, Harris AW, Pinkert CA, Corcoran LM, Alexander WS, Cory S, Palmiter RD, Brinster RL. The c-myc oncogene driven by immunoglobulin enhancers induces lymphoid malignancy in transgenic mice. Nature. 1985;318:533–538. - "VSports注册入口" PubMed
    1. Bodner SM, Naeve CW, Rakestraw KM, Jones BG, Valentine VA, Valentine MB, Luthardt FW, Willman CL, Raimondi SC, Downing JR, et al. Cloning and chromosomal localization of the gene encoding human cyclin D-binding Myb-like protein (hDMP1) Gene. 1999;229:223–238. - PubMed (V体育官网)
    1. Chin L, Pomerantz J, Polsky D, Jacobson M, Cohen C, Cardon-Cardo C, Horner JW, II, DePinho RA. Cooperative effects of INK4a and ras in melanoma susceptibility in vivo. Genes & Dev. 1997;11:2822–2834. - PMC - PubMed
    1. Eischen CM, Weber JD, Roussel MF, Sherr CJ, Cleveland JL. Disruption of the ARF–Mdm2–p53 tumor suppressor pathway in Myc-induced lymphomagenesis. Genes & Dev. 1999;13:2658–2669. - PMC - PubMed
    1. Esteller M, Corn PG, Baylin SB, Herman JG. A gene hypermethylation profile of human cancer. Cancer Res. 2001;61:3225–3229. - PubMed

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