Document Detail


Fibroblast growth factor 8 increases breast cancer cell growth by promoting cell cycle progression and by protecting against cell death.
MedLine Citation:
PMID:  19962979     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Fibroblast growth factor 8 (FGF-8) is expressed in a large proportion of breast cancers, whereas its level in normal mammary gland epithelium is low. Previous studies have shown that FGF-8b stimulates breast cancer cell growth in vitro and in vivo. To explore the mechanisms by which FGF-8b promotes growth, we studied its effects on cell cycle regulatory proteins and signalling pathways in mouse S115 and human MCF-7 breast cancer cells. We also studied the effect of FGF-8b on cell survival. FGF-8b induced cell cycle progression and up-regulated particularly cyclin D1 mRNA and protein in S115 cells. Silencing cyclin D1 with siRNA inhibited most but not all FGF-8b-induced proliferation. Inhibition of the FGF-8b-activated ERK/MAPK pathway decreased FGF-8b-stimulated proliferation. Blocking the constitutively active PI3K/Akt and p38 MAPK pathways also lowered FGF-8b-induced cyclin D1 expression and proliferation. Corresponding results were obtained in MCF-7 cells. In S115 and MCF-7 mouse tumours, FGF-8b increased cyclin D1 and Ki67 levels. Moreover, FGF-8b opposed staurosporine-induced S115 cell death which effect was blocked by inhibiting the PI3K/Akt pathway but not the ERK/MAPK pathway. In conclusion, our results suggest that FGF-8b increases breast cancer cell growth both by stimulating cell cycle progression and by protecting against cell death.
Authors:
Emeli M Nilsson; Leon J S Brokken; Pirkko L H?rk?nen
Related Documents :
8980229 - Dacapo, a cyclin-dependent kinase inhibitor, stops cell proliferation during drosophila...
8207059 - Cyclin-like accumulation and loss of the putative kinetochore motor cenp-e results from...
15796209 - Cell cycle and apoptosis deregulation in classical hodgkin lymphomas.
10194549 - Differential effects of ucn-01, staurosporine and cgp 41 251 on cell cycle progression ...
15922479 - Induction of anti-proliferative mechanisms in hepatitis b virus producing cells.
15817149 - Expression of progesterone receptor b is associated with g0/g1 arrest of the cell cycle...
10748199 - Regulation of membrane-type-1 matrix metalloproteinase activity by its cytoplasmic domain.
2960419 - T cell subsets in multiple sclerosis. gradients at plaque borders and differences in no...
19147009 - The primary cilium coordinates signaling pathways in cell cycle control and migration d...
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-12-04
Journal Detail:
Title:  Experimental cell research     Volume:  316     ISSN:  1090-2422     ISO Abbreviation:  Exp. Cell Res.     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-02-22     Completed Date:  2010-03-25     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0373226     Medline TA:  Exp Cell Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  800-12     Citation Subset:  IM    
Copyright Information:
2009 Elsevier Inc. All rights reserved.
Affiliation:
Department of Laboratory Medicine, Tumour Biology, Lund University, CRC, Building 91, Plan 10, Entrance 72, UMAS, 20502 Malm?, Sweden. Emeli.Nilsson@med.lu.se
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
1-Phosphatidylinositol 3-Kinase / metabolism
Animals
Breast Neoplasms / metabolism*,  physiopathology
Cell Cycle / physiology*
Cell Death / physiology*
Cell Line, Tumor
Cell Proliferation
Cyclin D1 / genetics,  metabolism
Enzyme Activation
Enzyme Inhibitors / metabolism
Female
Fibroblast Growth Factor 8 / genetics,  metabolism*
Humans
Mice
Mice, Nude
Protein Isoforms / genetics,  metabolism*
Proto-Oncogene Proteins c-akt / metabolism
RNA, Small Interfering / genetics,  metabolism
Signal Transduction / physiology
p38 Mitogen-Activated Protein Kinases / metabolism
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Protein Isoforms; 0/RNA, Small Interfering; 136601-57-5/Cyclin D1; 148997-75-5/Fibroblast Growth Factor 8; EC 2.7.1.137/1-Phosphatidylinositol 3-Kinase; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases

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


Previous Document:  Leukemia inhibitory factor dependent increase in myoblast cell number is associated with phosphotidy...
Next Document:  A conserved peptide motif in Raver2 mediates its interaction with the polypyrimidine tract-binding p...