Document Detail


Stimulation of the bradykinin B(1) receptor induces the proliferation of estrogen-sensitive breast cancer cells and activates the ERK1/2 signaling pathway.
MedLine Citation:
PMID:  19184415     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Kinin peptides exert multiple biological effects by binding to two types of G protein-coupled receptors known as B(1) (B(1)R) and B(2) receptors. Expression of the B(1)R in human breast cancer was recently reported, but up to now the consequences of its stimulation are unknown. Our aims were (1) to investigate the capacity of B(1)R to trigger cell proliferation in breast cancer cells, (2) to explore some of the downstream events occurring after B(1)R stimulation that may be linked to cell proliferation, and (3) to determine whether human breast tumors express potentially active B(1)R assessed by the binding of a radiolabeled agonist. Breast cancer cells expressed both the mRNA and the immunoreactive protein of B(1)R that once stimulated triggered cell proliferation at nanomolar concentrations of the ligand. Inhibitor studies suggested that the proliferative effects depend on the activity of epidermal growth factor receptor and subsequent ERK1/2 mitogen-activated protein kinases phosphorylation. B(1)R binding sites, were detected in 3/4 fibroadenomas, in 4/4 ductal carcinomas in situ and in 11/13 invasive ductal carcinomas. The B(1)R-epidermal growth factor receptor crosstalk may be a key interaction that maintains tumor growth, and antagonism of B(1)R may be a valuable alternative for the treatment of breast cancer.
Authors:
Luis Molina; Carola E Matus; Angel Astroza; Francisca Pavicic; Eugenio Tapia; Cesar Toledo; Juan A Perez; Francisco Nualart; Carlos B Gonzalez; Rafael A Burgos; Carlos D Figueroa; Pamela Ehrenfeld; Maria T Poblete
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-01-28
Journal Detail:
Title:  Breast cancer research and treatment     Volume:  118     ISSN:  1573-7217     ISO Abbreviation:  Breast Cancer Res. Treat.     Publication Date:  2009 Dec 
Date Detail:
Created Date:  2009-11-10     Completed Date:  2010-01-22     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8111104     Medline TA:  Breast Cancer Res Treat     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  499-510     Citation Subset:  IM    
Affiliation:
Laboratorio de Patologia Celular, Instituto de Anatomia, Histologia y Patologia, Universidad Austral de Chile, Valdivia, Chile.
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MeSH Terms
Descriptor/Qualifier:
Autoradiography
Blotting, Western
Breast Neoplasms / metabolism*,  pathology
Cell Line, Tumor
Cell Proliferation
Enzyme Activation / physiology
Extracellular Signal-Regulated MAP Kinases / metabolism*
Female
Gene Expression
Gene Expression Profiling
Humans
Immunohistochemistry
MAP Kinase Signaling System / physiology*
Receptor Cross-Talk / physiology*
Receptor, Bradykinin B1 / metabolism*
Receptor, Epidermal Growth Factor / metabolism
Reverse Transcriptase Polymerase Chain Reaction
Chemical
Reg. No./Substance:
0/Receptor, Bradykinin B1; EC 2.7.10.1/Receptor, Epidermal Growth Factor; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases

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