Document Detail


Twist1-mediated adriamycin-induced epithelial-mesenchymal transition relates to multidrug resistance and invasive potential in breast cancer cells.
MedLine Citation:
PMID:  19336515     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: Besides its therapeutic effects, chemotherapeutic agents also enhance the malignancy of treated cancers in clinical situations. Recently, epithelial-mesenchymal transition (EMT) has attracted attention in studies of tumor progression. We aimed to test whether transient Adriamycin treatment induces EMT and apoptosis simultaneously in cancer cells, clarify why the same type of cells responds differentially (i.e., apoptosis, EMT) to Adriamycin treatment, and elucidate the role of Twist1, the master regulator of EMT, in this process. EXPERIMENTAL DESIGN: In unsynchronized MCF7 cells or cells synchronized at different phases, apoptosis, EMT, and concurrent events [multidrug resistance (MDR) and tumor invasion] after Adriamycin or/and Twist1 small interfering RNA treatment were examined in vitro and in vivo. The Adriamycin-induced Twist1 expression and the interaction of Twist1 with p53-Mdm2 were examined by immunoblotting and immunoprecipitation, respectively. RESULTS: We showed in vitro that Adriamycin induced EMT and apoptosis simultaneously in a cell cycle-dependent manner. Only the cells undergoing EMT displayed enhanced invasion and MDR. Twist1 depletion completely blocked the mesenchymal transformation, partially reversed MDR, and greatly abolished invasion induced by Adriamycin. Also, we confirmed in vivo that Twist1 RNA interference improved the efficacy of Adriamycin for breast cancers. Further, Twist1 reduction in Adriamycin-treated cells promoted p53-dependent p21 induction and disrupted the association of p53 with Mdm2. CONCLUSIONS: Our studies show the diverse responses to Adriamycin treatment in cells at different phases, suggest an unrecognized role of EMT in regulating MDR and invasion, and show the efficacy of Twist1 RNA interference in Adriamycin-based chemotherapies for breast cancer.
Authors:
Qing-Quan Li; Jing-Da Xu; Wen-Juan Wang; Xi-Xi Cao; Qi Chen; Feng Tang; Zhong-Qing Chen; Xiu-Ping Liu; Zu-De Xu
Related Documents :
15896345 - Reversal of in vitro cellular mrp1 and mrp2 mediated vincristine resistance by the flav...
17070665 - Autophagy-mediated chemosensitizing effect of the plant alkaloid voacamine on multidrug...
1370765 - Reversal of multidrug resistance by an immunosuppressive agent fk-506.
12830325 - In vivo and in vitro multitracer analyses of p-glycoprotein expression-related multidru...
22395235 - Effect of tgf-β on gli2 expression in hl60 and u937 cell lines.
11021515 - Sertoli cells as a target for reproductive hazards.
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-03-31
Journal Detail:
Title:  Clinical cancer research : an official journal of the American Association for Cancer Research     Volume:  15     ISSN:  1078-0432     ISO Abbreviation:  Clin. Cancer Res.     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-04-16     Completed Date:  2009-06-04     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9502500     Medline TA:  Clin Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2657-65     Citation Subset:  IM    
Affiliation:
Department of Pathology, Shanghai Medical College, Shanghai, China.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Antibiotics, Antineoplastic / adverse effects*,  pharmacology
Apoptosis / drug effects,  physiology
Breast Neoplasms / metabolism,  pathology*
Cell Line, Tumor
Cyclin-Dependent Kinase Inhibitor p21 / metabolism
Doxorubicin / adverse effects*,  pharmacology
Drug Resistance, Multiple / drug effects*
Drug Resistance, Neoplasm / drug effects*
Epithelial Cells / drug effects,  metabolism,  pathology
Humans
Kaplan-Meiers Estimate
Mesoderm / drug effects,  metabolism,  pathology
Mice
Mice, Nude
Neoplasm Invasiveness
Nuclear Proteins / genetics,  metabolism*
Proto-Oncogene Proteins c-mdm2 / metabolism
RNA, Small Interfering / metabolism
Tumor Suppressor Protein p53 / metabolism
Twist Transcription Factor / genetics,  metabolism*
Chemical
Reg. No./Substance:
0/Antibiotics, Antineoplastic; 0/CDKN1A protein, human; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Nuclear Proteins; 0/RNA, Small Interfering; 0/TWIST1 protein, human; 0/Tumor Suppressor Protein p53; 0/Twist Transcription Factor; 23214-92-8/Doxorubicin; EC 6.3.2.19/MDM2 protein, human; EC 6.3.2.19/Proto-Oncogene Proteins c-mdm2

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


Previous Document:  Inhaled Growth Hormone (GH) Compared with Subcutaneous GH in Children with GH Deficiency: Pharmacoki...
Next Document:  Development and characterization of a novel in vivo model of carcinoid syndrome.