Document Detail


A novel tumor suppressor network in squamous malignancies.
MedLine Citation:
PMID:  23145321     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The specific ablation of Rb1 gene in stratified epithelia (Rb(F/F);K14cre) promotes proliferation and altered differentiation but is insufficient to produce spontaneous tumors. The pRb relative, p107, compensates some of the functions of pRb in these tissues; however, Rb(F/F);K14cre;p107(-/-) mice die postnatally. Here we show, using an inducible mouse model (Rb(F/F);K14creER(TM)), that p107 exerts specific tumor suppressor functions in the absence of pRb in stratified epithelia. The simultaneous absence of pRb and p107 produces impaired p53 transcriptional functions and reduction of Pten expression, allowing spontaneous squamous carcinoma development. These tumors display significant overlap with human squamous carcinomas, supporting that Rb(F/F);K14creER(TM);p107(-/-) mice might constitute a new model for these malignancies. Remarkably tumor development in vivo is partially alleviated by mTOR inhibition. These data demonstrate the existence of a previously unreported functional connection between pRb, Pten and p53 tumor suppressors, through p107, of a particular relevance in squamous tumor development.
Authors:
Clotilde Costa; Mirentxu Santos; Carmen Segrelles; Marta Dueñas; M Fernanda Lara; Xabier Agirre; Felipe Prosper; Ramón García-Escudero; Jesús M Paramio
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-11-09
Journal Detail:
Title:  Scientific reports     Volume:  2     ISSN:  2045-2322     ISO Abbreviation:  Sci Rep     Publication Date:  2012  
Date Detail:
Created Date:  2012-11-12     Completed Date:  2013-05-23     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  101563288     Medline TA:  Sci Rep     Country:  England    
Other Details:
Languages:  eng     Pagination:  828     Citation Subset:  IM    
Affiliation:
Molecular Oncology Unit, Department of Basic Research, CIEMAT (Ed 70A), Ave Complutense 40. 28040 Madrid, Spain.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Differentiation
Cell Proliferation
Cell Transformation, Neoplastic
Gene Regulatory Networks / genetics
Genes, Tumor Suppressor
Humans
Mice
Neoplasms, Squamous Cell* / genetics,  metabolism
PTEN Phosphohydrolase / genetics,  metabolism
Retinoblastoma Protein* / genetics,  metabolism
Retinoblastoma-Like Protein p107* / genetics,  metabolism
TOR Serine-Threonine Kinases / antagonists & inhibitors
Tumor Suppressor Protein p53* / genetics
Chemical
Reg. No./Substance:
0/Rbl1 protein, mouse; 0/Retinoblastoma Protein; 0/Retinoblastoma-Like Protein p107; 0/Tumor Suppressor Protein p53; EC 2.7.1.1/TOR Serine-Threonine Kinases; EC 2.7.1.1/mTOR protein, mouse; EC 3.1.3.48/Pten protein, mouse; EC 3.1.3.67/PTEN Phosphohydrolase
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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