Document Detail

Tumorigenicity of MCF-7 human breast cancer cells lacking the p38α mitogen-activated protein kinase.
MedLine Citation:
PMID:  20974639     Owner:  NLM     Status:  MEDLINE    
We have generated cell lines with significantly reduced expression of the p38 mitogen-activated protein kinase (p38 MAPK), Min-p38 MAPK cells, and used these cells to investigate p38 MAPK's role in tumorigenesis of breast cancer cells. MCF-7 cells were stably transfected with a plasmid producing small interfering RNA that inhibited the expression of p38 MAPK. Control cells were stably transfected with the same plasmid producing non-interfering RNA. The reduction in the p38 MAPK activity caused a significant increase in the expressions of estrogen receptor-α (ERα) and the progesterone receptor, but eliminated the expression of ERβ. Min-p38 MAPK cells showed an enhanced overall growth response to 17β-estradiol (E₂), whereas GH plus epidermal growth factor were largely ineffective growth stimulators in these cells compared to controls. Although the long-term net growth rate of the Min-p38 MAPK cells was increased in response to E₂, their proliferation rate was lower compared to controls in short-term cultures. However, the Min-p38 MAPK cells did show a significant decreased rate of apoptosis after E₂ treatment and a reduction in the basal phosphorylation of p53 tumor suppressor protein compared to controls. When the Min-p38 MAPK cells were xenografted into E₂-treated athymic nude mice, their tumorigenicity was enhanced compared to control cells. Increased tumorigenicity of Min-p38 MAPK cells was caused mainly by a decrease in the apoptosis rate indicating that the lack of the p38 MAPK caused an imbalance to increase the ERα:ERβ ratio and a reduction in the activity of the p53 tumor suppressor protein.
Rhone A Mendoza; Emily E Moody; Marlene I Enriquez; Sylvia M Mejia; Gudmundur Thordarson
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-10-25
Journal Detail:
Title:  The Journal of endocrinology     Volume:  208     ISSN:  1479-6805     ISO Abbreviation:  J. Endocrinol.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2010-12-07     Completed Date:  2011-01-11     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  0375363     Medline TA:  J Endocrinol     Country:  England    
Other Details:
Languages:  eng     Pagination:  11-9     Citation Subset:  IM    
Department of Biomedical Sciences, Paul L. Foster School of Medicine, Center of Excellence in Cancer Research, Texas Tech University Health Sciences Center, 5001 El Paso Drive, El Paso, Texas 79905, USA.
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MeSH Terms
Analysis of Variance
Apoptosis / drug effects,  physiology
Blotting, Western
Cell Count
Cell Line, Tumor
Cell Proliferation / drug effects*
Enzyme-Linked Immunosorbent Assay
Estradiol / pharmacology
Estrogen Receptor alpha / genetics*,  metabolism
Estrogen Receptor beta / genetics*,  metabolism
Mice, Nude
Mitogen-Activated Protein Kinase 14 / genetics*,  metabolism
Neoplasm Transplantation
Receptors, Progesterone / genetics*,  metabolism
Tumor Cells, Cultured
Tumor Suppressor Protein p53 / genetics,  metabolism
Grant Support
R03 CA128067-01A1/CA/NCI NIH HHS; R03 CA128067-02/CA/NCI NIH HHS; R03 CA128067-02S1/CA/NCI NIH HHS; R03 CA128067-03/CA/NCI NIH HHS; R03CA128067/CA/NCI NIH HHS; R03CA128067-02S1/CA/NCI NIH HHS
Reg. No./Substance:
0/Estrogen Receptor alpha; 0/Estrogen Receptor beta; 0/Receptors, Progesterone; 0/Tumor Suppressor Protein p53; 50-28-2/Estradiol; EC Protein Kinase 14

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