Linked Life Data

15734997

Source:http://linkedlifedata.com/resource/pubmed/id/15734997

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2005-2-28
pubmed:abstractText
Proteins controlling cell growth, differentiation, apoptosis, and oncogenic stress are often deregulated in tumor cells. However, whether such deregulations affect tumor behavior remains poorly understood in many tumor types. We recently showed that the urothelium-specific expression of activated H-ras and SV40 T antigen in transgenic mice produced two distinctive types of tumors strongly resembling the human superficial papillary tumors and carcinoma in situ of the bladder, respectively. Here we assessed the expression of a key set of cell cycle regulators in these mouse tumors and in a new transgenic line expressing a cyclin D1 oncogene in the urothelium. We found that urothelia of the wild-type and cyclin D1 transgenic mice exhibited a profile of cell cycle regulators found in quiescent (G(0)) cells, indicating that urothelium overexpressing the cyclin D1 (an 8-fold increase) is reminiscent of normal urothelium and remains slow-cycling. Low-grade superficial papillary tumors induced by activated H-ras had no detectable Rb family proteins (Rb, p107, and p130) and late cell cycle cyclins and kinases (cyclin A, E, and CDK1), but had increased level of p16, p53, and MDM2. These data suggest that the inactivation of the Rb pathway plays an important role in H-ras-induced superficial papillary tumors and that oncogenic H-ras can induce a compensatory activation of alternative tumor suppressor pathways. In contrast, carcinoma in situ of the bladder induced by SV40 T antigen had increased expression of cell cycle regulators mainly active in post-G(1) phases. The fact that phenotypically different bladder tumors exhibit different patterns of cell cycle regulators may explain why these tumors have different propensity to progress to invasive tumors. Our results indicate that the transgenic mouse models can be used not only for studying tumorigenesis but also for evaluating therapeutic strategies that target specific cell cycle regulators.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
65
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1150-7
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:15734997-Animals, pubmed-meshheading:15734997-Antigens, Polyomavirus Transforming, pubmed-meshheading:15734997-Carcinoma, Papillary, pubmed-meshheading:15734997-Cell Cycle, pubmed-meshheading:15734997-Cell Cycle Proteins, pubmed-meshheading:15734997-Cyclin D1, pubmed-meshheading:15734997-Cyclin-Dependent Kinase Inhibitor p21, pubmed-meshheading:15734997-Cyclin-Dependent Kinase Inhibitor p27, pubmed-meshheading:15734997-Genes, ras, pubmed-meshheading:15734997-Hyperplasia, pubmed-meshheading:15734997-Mice, pubmed-meshheading:15734997-Mice, Transgenic, pubmed-meshheading:15734997-Proliferating Cell Nuclear Antigen, pubmed-meshheading:15734997-Retinoblastoma Protein, pubmed-meshheading:15734997-Tumor Suppressor Proteins, pubmed-meshheading:15734997-Urinary Bladder Neoplasms, pubmed-meshheading:15734997-Urothelium
pubmed:year
2005
pubmed:articleTitle
Differential expression of cell cycle regulators in phenotypic variants of transgenically induced bladder tumors: implications for tumor behavior.
pubmed:affiliation
Department of Pathology, New York University Cancer Institute, New York, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't