TEAD1 and c-Cbl are novel prostate basal cell markers that correlate with poor clinical outcome in prostate cancer.
Prostate cancer is the most frequently diagnosed male cancer, and its clinical outcome is difficult to predict. The disease may involve the inappropriate expression of genes that normally control the proliferation of epithelial cells in the basal layer and their differentiation into luminal cells. Our aim was to identify novel basal cell markers and assess their prognostic and functional significance in prostate cancer. RNA from basal and luminal cells isolated from benign tissue by immunoguided laser-capture microdissection was subjected to expression profiling. We identified 112 and 267 genes defining basal and luminal populations, respectively. The transcription factor TEAD1 and the ubiquitin ligase c-Cbl were identified as novel basal cell markers. Knockdown of either marker using siRNA in prostate cell lines led to decreased cell growth in PC3 and disrupted acinar formation in a 3D culture system of RWPE1. Analyses of prostate cancer tissue microarray staining established that increased protein levels of either marker were associated with decreased patient survival independent of other clinicopathological metrics. These data are consistent with basal features impacting on the development and clinical course of prostate cancers.
Knight
J F
JF
Department of Molecular Carcinogenesis, The Bob Champion Prostate Stem Cell Team, The Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK.
Shepherd
C J
CJ
Rizzo
S
S
Brewer
D
D
Jhavar
S
S
Dodson
A R
AR
Cooper
C S
CS
Eeles
R
R
Falconer
A
A
Kovacs
G
G
Garrett
M D
MD
Norman
A R
AR
Shipley
J
J
Hudson
D L
DL
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D042282:Microdissection; D008875:Middle Aged; D009687:Nuclear Proteins / Q000096:biosynthesis*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D050721:Proto-Oncogene Proteins c-cbl / Q000096:biosynthesis*; D034741:RNA, Small Interfering; D000091262:TEA Domain Transcription Factors; D046888:Tissue Array Analysis; D014157:Transcription Factors / Q000096:biosynthesis*; D014162:Transfection
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D000091262:TEA Domain Transcription Factors; C057182:TEAD1 protein, human; D014157:Transcription Factors; D050721:Proto-Oncogene Proteins c-cbl; C067419:CBL protein, human