Document Detail

Pituitary tumor transforming gene causes aneuploidy and p53-dependent and p53-independent apoptosis.
MedLine Citation:
PMID:  11013229     Owner:  NLM     Status:  MEDLINE    
The pituitary tumor transforming gene, PTTG, is abundantly expressed in several neoplasms. We recently showed that PTTG overexpression is associated with apoptosis and therefore have now studied the role of p53 in this process. In MCF-7 breast cancer cells that express wild type p53, PTTG overexpression caused apoptosis. p53 was translocated to the nuclei in cells expressing PTTG. Overexpression of p53, along with PTTG, augmented apoptosis, whereas expression of the human papillomavirus E6 protein inhibited PTTG-induced apoptosis. In MG-63 osteosarcoma cells that are deficient in p53, PTTG caused cell cycle arrest and subsequent apoptosis that was inhibited by caspase inhibitors. A proteasome inhibitor augmented PTTG expression in stable PTTG transfectants, suggesting that down-regulated PTTG expression is required for cell survival. Finally, MG-63 cells expressing PTTG showed signs of aneuploidy including the presence of micronuclei and multiple nuclei. These results indicate that PTTG overexpression causes p53-dependent and p53-independent apoptosis. In the absence of p53, PTTG causes aneuploidy. These results may provide a mechanism for PTTG-induced tumorigenesis whereby PTTG mediates aneuploidy and subsequent cell transformation.
R Yu; A P Heaney; W Lu; J Chen; S Melmed
Related Documents :
17419939 - Structural biology of the tumor suppressor p53 and cancer-associated mutants.
11462029 - Inhibition of p53 tumor suppressor by viral interferon regulatory factor.
10951339 - P53 mutations do not predict response to paclitaxel in metastatic nonsmall cell lung ca...
12554679 - Ets2 overexpression in transgenic models and in down syndrome predisposes to apoptosis ...
20212049 - Characterization of functional domains necessary for mutant p53 gain of function.
12170089 - Immunohistochemical p53 expression patterns in sarcomatoid carcinomas of the upper resp...
12478659 - Multigene analysis of rb pathway and apoptosis control in esophageal squamous cell carc...
19444819 - Up-regulation of the inflammatory-reparative phenotype in human prostate carcinoma.
16533769 - The lysyl oxidase lox is absent in basal and squamous cell carcinomas and its knockdown...
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  275     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2000 Nov 
Date Detail:
Created Date:  2001-01-08     Completed Date:  2001-01-08     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  36502-5     Citation Subset:  IM    
Cedars-Sinai Research Institute, UCLA School of Medicine, Los Angeles, California 90048, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Breast Neoplasms / metabolism
Neoplasm Proteins / genetics*
Osteosarcoma / metabolism
Trans-Activators / genetics*
Tumor Cells, Cultured
Tumor Suppressor Protein p53 / physiology*
Grant Support
Reg. No./Substance:
0/Neoplasm Proteins; 0/Trans-Activators; 0/Tumor Suppressor Protein p53; 0/pituitary tumor-transforming proteins

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

Previous Document:  Misinsertion and bypass of thymine-thymine dimers by human DNA polymerase iota.
Next Document:  Direct binding of activated c-Src to the beta 3-adrenergic receptor is required for MAP kinase activ...