Table 5.
Contribution of Pim1 overexpression to tumorigenesis in double-transgenic mouse models.
| Mouse model | Single-transgenic phenotype | Double-transgenic phenotype |
|---|---|---|
| E2a-Pbx1; H2K-pim1 | E2a-Pbx1: 13% incidence lymphoma at 24 weeks H2K-pim1: no tumors in 1 year | Lethargy, respiratory distress, and abdominal distension due to aggressive lymphomas, 100% incidence at 13 weeks (65) |
| Eμ-c-myc;Eμ-pim1 | EμPim1: enlargement of the spleen | Pre-B-cell leukemia in uterus; 100% incidence (28) |
| Monoclonal T-cell lymphoma; 10% incidence at 34 weeks of age | ||
| Eμ-c-myc: pre-B-cell lymphomas; 75% incidence latency between 10 and 53 weeks of age | ||
| Eμ-L-myc;Eμ-pim1 | Eμ-pim1: enlargement of the spleen | T-cell lymphomas; 80% incidence at 12 weeks (49) |
| Monoclonal T-cell lymphoma; 10% incidence at 34 weeks of age | ||
| Eμ-L-myc: T-, B-, and pre-B-lymphomas; 8% incidence at 53 weeks of age | ||
| Eμ-N-myc;Eμ-pim1 | Eμ-pim1: enlargement of the spleen | B- and pre-B-lymphomas; 95% incidence at 5 weeks of age (49) |
| Monoclonal T-cell lymphoma; 10% incidence at 34 weeks of age | ||
| Eμ-N-myc: B- and pre-B-lymphomas; 50% incidence between 13 and 16 weeks of age | ||
| Lck-gfi-1; Eμ-pim1 | Lck-gfi-1: developmental block of early T-cell development leading to a loss of thymic cellularity. T-cell lymphomas; 15% incidence at 28.5 weeks of age | Thymus cellularity restored. T-cell lymphomas; 82% incidence at 16.2 weeks of age (50, 75) |
| Eμ-pim1: enlargement of the spleen | ||
| Monoclonal T-cell lymphoma; 10% incidence at 34 weeks of age | ||
| CD2-runx2;Eμ-pim1 | CD2-Runx2: T-cell lymphomas; 23% incidence at 53 weeks | T-cell lymphoma; 66% incidence at 36 weeks (55) |
| Eμ-Pim1: enlargement of the spleen | ||
| Monoclonal T-cell lymphoma; 10% incidence at 34 weeks of age | ||
| CD2-runx2;Eμ-pim1; CD2-c-myc | CD2-Runx2: T-cell lymphomas; 23% incidence at 53 weeks | T-cell lymphoma; 100% at 5 weeks (55) |
| Eμ-pim1: enlargement of the spleen | ||
| Monoclonal T-cell lymphoma; 10% incidence at 34 weeks of age | ||
| CD2-c-myc: T-cell lymphomas; 100% incidence at 7 weeks | ||
| Eμ-pim1; γc−/− | Eμpim1: enlargement of the spleen | Thymus cellularity restored (69) |
| Eμ-pim1;IL17−/− | Monoclonal T-cell lymphoma; 10% incidence at 34 weeks of age | |
| γc−/−and IL17−/−: significant reduction in thymocyte number | ||
| Eμ-pim1;Eμ-pp-Frat1 | Eμpim1: T-cell lymphoma; 12% incidence at 26 weeks of age | T-cell lymphoma; 50% incidence at 26 weeks. High levels of expression of c-myc (67) |
| Eμ-pp-Frat1: no tumors at 26 weeks of age | ||
| Eμ-pim1;Rag3−/− | Eμpim1: enlargement of the spleen | Thymus cellularity restored in an age-dependent manner in Rag3−/− but not CD3γ−/−mice (69) |
| Eμ-pim1; CD3γ−/− | Monoclonal T-cell lymphoma; 10% incidence at 34 weeks of age | |
| Rag3−/− and CD3γ−/−; differentiation block at the CD4−8−25+44− stage of αβ T-cell development | ||
| Eμ-c-myc;Eμ-pim2 | Eμpim2: T-cell lymphoma; 40% incidence after 53 weeks | Severe leukemia, some harboring simultaneous T-cell lymphoma; 100% incidence at 3–4 weeks of age (29) |
| Eμ-c-myc: Pre-B-cell lymphomas; 75% incidence and latency between 10 and 53 weeks of age | ||
| Eμ-Myc HPCs expressing AKT, Pim2, or vector inoculated into lethally irradiated syngeneic wild-type recipients |
Eμ-Myc: HPCs with vector; pre-B-cell lymphomas with 20% incidence at 14 weeks Eμ-Myc; Arf −/− tumors responded to doxorubicin or rapamycin but responded to the combination |
Eμ-Myc HPCs with Pim2: pre-B-cell lymphomas with 100% incidence at 10.7 weeks of age. Resistant to doxorubicin, rapamycin, and combination treatment |
| Eμ-Myc HPCs with AKT: pre-B-cell lymphomas with 100% incidence at 12 weeks. Resistant to doxorubicin and rapamycin but sensitive to combination treatment (63) | ||
| Eμ-Myc: Tsc2−/− HPCs expressing Pim2 or vector inoculated into lethally irradiated, syngeneic wild-type recipients | Eμ-Myc: Tsc2−/− tumors treated with rapamycin relapse-free up to 3 weeks | Eμ-Myc: Tsc2−/− with Pim2 tumors treated with rapamycin resistant or relapsed free up to 2 weeks, treatment with silvestrol delayed relapse to 2.7 weeks (63) |
| pim1;PSA61-Cre; pten+/− | Prostate and bladder epithelium | Hormone-induced high-grade mPIN lesions in cooperation with pten loss; no cooperation in aging-induced mPIN. Increased inflammation surrounding target tissues leading to pyelonephritis with 100% penetrance in 16-week-old mice (33) |
| One round of hormone treatment induced high-grade bladder hyperplasia in cooperation with pten loss | ||
| 86% Penetrance in 16 weeks old mice (34) |