Document Detail


Stathmin/oncoprotein 18, a microtubule regulatory protein, is required for survival of both normal and cancer cell lines lacking the tumor suppressor, p53.
MedLine Citation:
PMID:  20200495     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Stathmin, a microtubule regulatory protein, is overexpressed in many cancers and required for survival of several cancer lines. In a study of breast cancer cell lines(1) proposed that stathmin is required for survival of cells lacking p53, but this hypothesis was not tested directly. Here we tested their hypothesis by examining cell survival in cells depleted of stathmin, p53 or both proteins. Comparing HCT116 colon cancer cell lines differing in TP53 genotype, stathmin depletion resulted in significant death only in cells lacking p53. As a second experimental system, we compared the effects of stathmin depletion from HeLa cells, which normally lack detectable levels of p53 due to expression of the HPV E6 protein. Stathmin depletion caused a large percentage of HeLa cells to die. Restoring p53, by depletion of HPV E6, rescued HeLa cells from stathmin-depletion induced death. Cleaved PARP was detected in HCT116(p53-/-) cells depleted of stathmin and cell death in stathmin-depleted HeLa cells was blocked by the caspase inhibitor Z-VAD-FMK, consistent with apoptotic death. The stathmin-dependent survival of cells lacking p53 was not confined to cancerous cells because both proteins were required for survival of normal human fibroblasts. In HCT116 and HeLa cells, depletion of both stathmin and p53 leads to a cell cycle delay through G(2). Our results demonstrate that stathmin is required for cell survival in cells lacking p53, suggesting that stathmin depletion could be used therapeutically to induce apoptosis in tumors without functional p53.
Authors:
Bruce K Carney; Lynne Cassimeris
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-05-08
Journal Detail:
Title:  Cancer biology & therapy     Volume:  9     ISSN:  1555-8576     ISO Abbreviation:  Cancer Biol. Ther.     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-08-16     Completed Date:  2010-12-07     Revised Date:  2013-02-05    
Medline Journal Info:
Nlm Unique ID:  101137842     Medline TA:  Cancer Biol Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  699-709     Citation Subset:  IM    
Affiliation:
Department of Biological Sciences, Lehigh University, Bethlehem, PA, USA.
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MeSH Terms
Descriptor/Qualifier:
Antibiotics, Antineoplastic / pharmacology
Apoptosis / drug effects
Blotting, Western
Cell Proliferation / drug effects
Cell Survival
Cells, Cultured
Colonic Neoplasms / metabolism*,  pathology*
Cytoskeletal Proteins / antagonists & inhibitors,  genetics,  metabolism
Doxorubicin / pharmacology
Fibroblasts / cytology*,  metabolism*
Fluorescent Antibody Technique
Genes, Tumor Suppressor
Humans
Muscle Proteins / antagonists & inhibitors,  genetics,  metabolism
Oncogene Proteins, Viral / antagonists & inhibitors,  genetics,  metabolism
Poly(ADP-ribose) Polymerases / genetics,  metabolism
RNA, Messenger / genetics
RNA, Small Interfering / pharmacology
Repressor Proteins / antagonists & inhibitors,  genetics,  metabolism
Reverse Transcriptase Polymerase Chain Reaction
Stathmin / physiology*
Tumor Suppressor Protein p53 / antagonists & inhibitors,  genetics,  metabolism*
Grant Support
ID/Acronym/Agency:
GM058025/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Antibiotics, Antineoplastic; 0/Cytoskeletal Proteins; 0/E6 protein, Human papillomavirus type 16; 0/Muscle Proteins; 0/Oncogene Proteins, Viral; 0/RNA, Messenger; 0/RNA, Small Interfering; 0/Repressor Proteins; 0/SMTN protein, human; 0/Stathmin; 0/TP53 protein, human; 0/Tumor Suppressor Protein p53; 23214-92-8/Doxorubicin; EC 2.4.2.30/Poly(ADP-ribose) Polymerases

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


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