Document Detail

Deletion of the olfactomedin 4 gene is associated with progression of human prostate cancer.
MedLine Citation:
PMID:  24070418     Owner:  NLM     Status:  MEDLINE    
The olfactomedin 4 (OLFM4) gene is located on chromosome 13q14.3, which frequently is deleted in human prostate cancer. However, direct genetic evidence of OLFM4 gene alteration in human prostate cancer has not yet been obtained. In this study, we investigated the genetics, protein expression, and functions of the OLFM4 gene in human prostate cancer. We found overall 25% deletions within the OLFM4 gene in cancerous epithelial cells compared with adjacent normal epithelial cells that were microdissected from 31 prostate cancer specimens using laser-capture microdissection and genomic DNA sequencing. We found 28% to 45% hemizygous and 15% to 57% homozygous deletions of the OLFM4 gene via fluorescence in situ hybridization analysis from 44 different prostate cancer patient samples. Moreover, homozygous deletion of the OLFM4 gene significantly correlated with advanced prostate cancer. By using immunohistochemical analysis of 162 prostate cancer tissue array samples representing a range of Gleason scores, we found that OLFM4 protein expression correlated inversely with advanced prostate cancer, consistent with the genetic results. We also showed that a truncated mutant of OLFM4 that lacks the olfactomedin domain eliminated suppression of PC-3 prostate cancer cell growth. Together, our findings indicate that OLFM4 is a novel candidate tumor-suppressor gene for chromosome 13q and may shed new light on strategies that could be used for the diagnosis, prognosis, and treatment of prostate cancer patients.
Hongzhen Li; Jaime Rodriguez-Canales; Wenli Liu; Jianqiong Zhu; Jeffrey C Hanson; Svetlana Pack; Zhengping Zhuang; Michael R Emmert-Buck; Griffin P Rodgers
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural    
Journal Detail:
Title:  The American journal of pathology     Volume:  183     ISSN:  1525-2191     ISO Abbreviation:  Am. J. Pathol.     Publication Date:  2013 Oct 
Date Detail:
Created Date:  2013-09-27     Completed Date:  2014-04-22     Revised Date:  2014-10-09    
Medline Journal Info:
Nlm Unique ID:  0370502     Medline TA:  Am J Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1329-38     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
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MeSH Terms
Autophagy / genetics
Base Sequence
Cathepsin D / metabolism
Cell Line, Tumor
Cell Proliferation
Disease Progression*
Gene Deletion*
Gene Expression Regulation, Neoplastic
Genome, Human / genetics
Granulocyte Colony-Stimulating Factor / chemistry,  genetics*,  metabolism
In Situ Hybridization, Fluorescence
Laser Capture Microdissection
Molecular Sequence Data
Mutant Proteins / metabolism
Neoplasm Staging
Polymorphism, Single Nucleotide / genetics
Prostatic Neoplasms / enzymology,  genetics*,  pathology*
Protein Structure, Tertiary
Tissue Array Analysis
Reg. No./Substance:
0/Mutant Proteins; 0/OLFM4 protein, human; 143011-72-7/Granulocyte Colony-Stimulating Factor; EC D

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