Document Detail

Intracrine PTHrP protects against serum starvation-induced apoptosis and regulates the cell cycle in MCF-7 breast cancer cells.
MedLine Citation:
PMID:  11796515     Owner:  NLM     Status:  MEDLINE    
PTHrP is secreted by breast cancer cells in vivo and in vitro. In the breast cancer cell line MCF-7, PTHrP overexpression is associated with increased mitogenesis. We used this cell line to study the mechanism for the proliferative effects of PTHrP. Clonal MCF-7 lines were established overexpressing wild-type PTHrP or PTHrP mutated in the nuclear localization signal (NLS). Mutation of the NLS negated the proliferative effects and nuclear trafficking of PTHrP, indicating that increased mitogenesis is mediated via an intracrine pathway. Cells overexpressing wild-type PTHrP were enriched in G2 + M stage of the cell cycle compared with cells overexpressing NLS-mutated PTHrP, indicating an intracrine role for PTHrP in cell cycle regulation. Wild-type PTHrP also protected MCF-7 cells from serum starvation-induced apoptosis. Cells overexpressing wild-type PTHrP showed significantly greater cell survival than cells overexpressing NLS-mutated PTHrP. The ratios of the apoptosis-regulating proteins Bcl-2 to Bax and Bcl-x(L) to Bax were higher in cells overexpressing wild-type, but not NLS-mutated, PTHrP compared with control cells. These findings suggest that the proliferative effects of PTHrP in breast cancer cells are mediated through regulation of the cell cycle and apoptosis, and that controlling PTHrP production in breast cancer may be therapeutically useful.
Veronica A Tovar Sepulveda; Xiaoli Shen; Miriam Falzon
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Endocrinology     Volume:  143     ISSN:  0013-7227     ISO Abbreviation:  Endocrinology     Publication Date:  2002 Feb 
Date Detail:
Created Date:  2002-01-17     Completed Date:  2002-02-28     Revised Date:  2006-06-29    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  596-606     Citation Subset:  AIM; IM    
Department of Pharmacology and Toxicology and Sealy Center for Molecular Science, University of Texas Medical Branch, Galveston, Texas 77555, USA.
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MeSH Terms
Apoptosis / drug effects*
Blotting, Northern
Breast Neoplasms / pathology*
Cell Count
Cell Cycle / drug effects
Cell Nucleus / physiology,  ultrastructure
Culture Media, Serum-Free
Flow Cytometry
Fluorescent Antibody Technique
Genes, bcl-2 / genetics
Mutation / genetics
Parathyroid Hormone-Related Protein
Plasmids / genetics
Proteins / genetics,  physiology*
RNA, Messenger / biosynthesis
Signal Transduction / physiology
Thymidine / metabolism
Tumor Cells, Cultured
Reg. No./Substance:
0/Culture Media, Serum-Free; 0/PTHLH protein, human; 0/Parathyroid Hormone-Related Protein; 0/Proteins; 0/RNA, Messenger; 50-89-5/Thymidine

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