Combined loss of p21(waf1/cip1) and p27(kip1) enhances tumorigenesis in mice
- PMID: 21876534
- DOI: 10.1038/labinvest.2011.133
Combined loss of p21(waf1/cip1) and p27(kip1) enhances tumorigenesis in mice
Abstract
The cell cycle inhibitors p21(Waf1/Cip1) and p27(Kip1) are frequently downregulated in many human cancers, and correlate with a worse prognosis. We show here that combined deficiency in p21 and p27 proteins in mice is linked to more aggressive spontaneous tumorigenesis, resulting in a decreased lifespan. The most common tumors developed in p21p27 double-null mice were endocrine, with a higher incidence of pituitary adenomas, pheochromocytomas and thyroid adenomas. The combined absence of p21 and p27 proteins delays the incidence of radiation-induced thymic lymphomas with a higher apoptotic rate, measured by active caspase-3 and cleaved PARP-1 immunoexpresion. These results provide experimental evidence for a cooperation of both cyclin-dependent kinase inhibitors in tumorigenesis in mice.
Similar articles
-
Loss of the cell cycle inhibitors p21(Cip1) and p27(Kip1) enhances tumorigenesis in knockout mouse models.Oncogene. 2002 Dec 5;21(55):8486-97. doi: 10.1038/sj.onc.1205946. Oncogene. 2002. PMID: 12466968
-
Gene delivery of cyclin-dependent kinase inhibitors p21Waf1 and p27Kip1 suppresses proliferation of MCF-7 breast cancer cells in vitro.Breast Cancer. 2014 Sep;21(5):614-23. doi: 10.1007/s12282-012-0438-y. Epub 2013 Jan 22. Breast Cancer. 2014. PMID: 23338153
-
Expression of p27(KIP1) and p21(WAF1/CIP1) in primary hepatocellular carcinoma: clinicopathologic correlation and survival analysis.Hum Pathol. 2001 Aug;32(8):778-84. doi: 10.1053/hupa.2001.27105. Hum Pathol. 2001. PMID: 11521219
-
Differential expression of forkhead box M1 and its downstream cyclin-dependent kinase inhibitors p27(kip1) and p21(waf1/cip1) in the diagnosis of pulmonary neuroendocrine tumours.Histopathology. 2012 Apr;60(5):731-9. doi: 10.1111/j.1365-2559.2011.04137.x. Epub 2012 Feb 1. Histopathology. 2012. PMID: 22296117
-
Ubiquitylation and proteasomal degradation of the p21(Cip1), p27(Kip1) and p57(Kip2) CDK inhibitors.Cell Cycle. 2010 Jun 15;9(12):2342-52. doi: 10.4161/cc.9.12.11988. Epub 2010 Jun 15. Cell Cycle. 2010. PMID: 20519948 Free PMC article. Review.
Cited by
-
Muti-omics integration analysis revealed molecular network alterations in human nonfunctional pituitary neuroendocrine tumors in the framework of 3P medicine.EPMA J. 2022 Feb 17;13(1):9-37. doi: 10.1007/s13167-022-00274-5. eCollection 2022 Mar. EPMA J. 2022. PMID: 35273657 Free PMC article. Review.
-
Absence of cyclin-dependent kinase inhibitor p27 or p18 increases efficiency of iPSC generation without induction of iPSC genomic instability.Cell Death Dis. 2019 Mar 20;10(4):271. doi: 10.1038/s41419-019-1502-8. Cell Death Dis. 2019. PMID: 30894510 Free PMC article.
-
PARP-2 sustains erythropoiesis in mice by limiting replicative stress in erythroid progenitors.Cell Death Differ. 2015 Jul;22(7):1144-57. doi: 10.1038/cdd.2014.202. Epub 2014 Dec 12. Cell Death Differ. 2015. PMID: 25501596 Free PMC article.
-
p21 in Cancer Research.Cancers (Basel). 2019 Aug 14;11(8):1178. doi: 10.3390/cancers11081178. Cancers (Basel). 2019. PMID: 31416295 Free PMC article. Review.
-
p21 and p27 a shared senescence history.Cell Cycle. 2014;13(11):1655-6. doi: 10.4161/cc.29147. Epub 2014 May 8. Cell Cycle. 2014. PMID: 24809983 Free PMC article. No abstract available.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Molecular Biology Databases
Research Materials
Miscellaneous
