| First Author | Damo LA | Year | 2005 |
| Journal | Mol Carcinog | Volume | 42 |
| Issue | 2 | Pages | 109-20 |
| PubMed ID | 15584024 | Mgi Jnum | J:95497 |
| Mgi Id | MGI:3526222 | Doi | 10.1002/mc.20068 |
| Citation | Damo LA, et al. (2005) Tumorigenesis in p27/p53- and p18/p53-double null mice: Functional collaboration between the pRb and p53 pathways. Mol Carcinog 42(2):109-20 |
| abstractText | Mice lacking both p18(Ink4c) and p27(Kip1) develop a tumor spectrum similar to pRb(+/-) mice, and loss of p53 function accelerates tumorigenesis in pRb(+/-) mice. We hypothesized that codeletion of either p18 or p27 in conjunction with p53 deletion will also accelerate tumorigenesis. Mice lacking both p18 and p53 develop several tumors not reported in either single null genotype, including hepatocellular carcinoma, testicular choriocarcinoma, hemangiosarcoma, leiomyosarcoma, fibrosarcoma, and osteosarcoma. Mice lacking both p27 and p53 exhibit a decreased lifespan and develop unique tumors, including papillary carcinoma of the colon, hemangiosarcoma, and leiomyosarcoma. In both p18/p53 and p27/p53 double null genotypes, the incidence and spectra of tissues that develop lymphoma are also increased, as compared to the single null genotypes. The development of p27/p53 double null colon tumors correlates with secondary changes in cell-cycle protein expression and CDK (cyclin-dependent kinase) activity, perhaps contributing to the progression of colorectal cancer. We concluded that p18 and p27 can, not only functionally collaborate with one another, but also can independently collaborate with p53 to modulate the cell cycle and suppress tumorigenesis in a tissue-specific manner. (c) 2004 Wiley-Liss, Inc. |
