Deletion of the olfactomedin 4 gene is associated with progression of human prostate cancer.
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.
Molecular and Clinical Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.
Hongzhen
H
Li
Jaime
J
Rodriguez-Canales
Wenli
W
Liu
Jianqiong
J
Zhu
Jeffrey C
JC
Hanson
Svetlana
S
Pack
Zhengping
Z
Zhuang
Michael R
MR
Emmert-Buck
Griffin P
GP
Rodgers
D001343:Autophagy / Q000235:genetics; D001483:Base Sequence; D002402:Cathepsin D / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human / Q000235:genetics; D016179:Granulocyte Colony-Stimulating Factor / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D006720:Homozygote; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D061346:Laser Capture Microdissection; D008297:Male; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000378:metabolism; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D017434:Protein Structure, Tertiary; D046888:Tissue Array Analysis
D050505:Mutant Proteins; C454127:OLFM4 protein, human; D016179:Granulocyte Colony-Stimulating Factor; D002402:Cathepsin D