Document Detail


Tumour cell survival mechanisms in lethal metastatic prostate cancer differ between bone and soft tissue metastases.
MedLine Citation:
PMID:  23420560     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The complexity of survival mechanisms in cancer cells from patients remains poorly understood. To obtain a comprehensive picture of tumour cell survival in lethal prostate cancer metastases, we examined five survival proteins that operate within three survival pathways in a cohort of 185 lethal metastatic prostate metastases obtained from 44 patients. The expression levels of BCL-2, BCL-XL, MCL-1, cytoplasmic survivin, nuclear survivin, and stathmin were measured by immunohistochemistry in a tissue microarray. Simultaneous expression of three or more proteins occurred in 81% of lethal prostate cancer metastases and BCL-2, cytoplasmic survivin and MCL-1 were co-expressed in 71% of metastatic sites. An unsupervised cluster analysis separated bone and soft tissue metastases according to patterns of survival protein expression. BCL-2, cytoplasmic survivin and MCL-1 had significantly higher expression in bone metastases (p < 10(-5)), while nuclear survivin was significantly higher in soft tissue metastases (p = 3 × 10(-14)). BCL-XL overexpression in soft tissue metastases almost reached significance (p = 0.09), while stathmin expression did not (p = 0.28). In addition, the expression of MCL-1 was significantly higher in AR-positive tumours. Neuroendocrine differentiation was not associated with specific survival pathways. These studies show that bone and soft tissue metastases from the same patient differ significantly in expression of a panel of survival proteins and that with regard to survival protein expression, expression is associated with the metastatic site and not the patient. Altogether, this suggests that optimal therapeutic inhibition may require combinations of drugs that target both bone and soft tissue-specific survival pathways.
Authors:
Canan Akfirat; Xiaotun Zhang; Aviva Ventura; Dror Berel; Mary E Colangelo; Cindy K Miranti; Maryla Krajewska; John C Reed; Celestia S Higano; Lawrence D True; Robert L Vessella; Colm Morrissey; Beatrice S Knudsen
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  The Journal of pathology     Volume:  230     ISSN:  1096-9896     ISO Abbreviation:  J. Pathol.     Publication Date:  2013 Jul 
Date Detail:
Created Date:  2013-06-10     Completed Date:  2013-08-27     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  0204634     Medline TA:  J Pathol     Country:  England    
Other Details:
Languages:  eng     Pagination:  291-7     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis
Bone Neoplasms / metabolism,  pathology,  secondary*
Cell Survival
Cluster Analysis
Cohort Studies
Disease Progression
Gene Expression Regulation, Neoplastic*
Humans
Inhibitor of Apoptosis Proteins / metabolism
Male
Mice
Myeloid Cell Leukemia Sequence 1 Protein
Prostatic Neoplasms / metabolism*,  pathology
Proto-Oncogene Proteins c-bcl-2 / metabolism
Rabbits
Soft Tissue Neoplasms / metabolism,  pathology,  secondary*
Stathmin / metabolism
Tissue Array Analysis
Tumor Markers, Biological / metabolism*
Tumor Microenvironment
Washington
bcl-X Protein / biosynthesis,  metabolism
Grant Support
ID/Acronym/Agency:
NCI-P50//PHS HHS; NCI-PO1CA085/CA/NCI NIH HHS; NCI-R21CA11/CA/NCI NIH HHS; NCI-R21CA152/CA/NCI NIH HHS; P01 CA085859/CA/NCI NIH HHS; P50 CA097186/CA/NCI NIH HHS; R01 CA154835/CA/NCI NIH HHS; R21 CA118592/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/BCL2L1 protein, human; 0/BIRC5 protein, human; 0/Inhibitor of Apoptosis Proteins; 0/Mcl1 protein, mouse; 0/Myeloid Cell Leukemia Sequence 1 Protein; 0/Proto-Oncogene Proteins c-bcl-2; 0/STMN1 protein, human; 0/Stathmin; 0/Tumor Markers, Biological; 0/bcl-X Protein
Comments/Corrections

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


Previous Document:  Surface initiated polymerization of a cationic monomer on inner surfaces of silica capillaries: Anal...
Next Document:  Theory of the spin Seebeck effect.