APC/CTNNB1 (beta-catenin) pathway alterations in human prostate cancers.
Genetic alterations serve as beacons for the involvement of specific pathways in tumorigenesis. It was previously shown that 5% of prostate tumors harbor CTNNB1 mutations, suggesting that this tumor type may involve a deregulated APC/CTNNB1 pathway. To explore this possibility further, we searched for mutations in genes implicated in this pathway in 22 samples that included cell lines, xenografts, and primary tumors. We identified seven alterations: two in CTNNB1, three in APC, and two in hTRCP1 (also known as BTRC) which controls the degradation of CTNNB1. Alterations in the CTNNB1 regulatory domain, APC, and hTRCP1 were mutually exclusive, consistent with their equivalent effects on CTNNB1 stability. These results suggest that CTNNB1 signaling plays a critical role in the development of a significant fraction of prostate cancers. Moreover, they provide the first evidence that hTRCP1 plays a role in human neoplasia.
Gerstein
Amy V
AV
Department of Pathology, Institute of Cancer Genetics, Columbia University, New York, New York, USA.
Almeida
Teresa Acosta
TA
Zhao
Guojing
G
Chess
Eric
E
Shih
Ie-Ming
IeM
Buhler
Kent
K
Pienta
Kenneth
K
Rubin
Mark A
MA
Vessella
Robert
R
Papadopoulos
Nickolas
N
D000818:Animals; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D005091:Exons / Q000235:genetics; D019204:GTP-Binding Proteins / Q000235:genetics; D017491:Genes, APC; D006801:Humans; D008297:Male; D051379:Mice; D009154:Mutation / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D015534:Trans-Activators; D014407:Tumor Cells, Cultured; D051176:beta Catenin; D044844:beta-Transducin Repeat-Containing Proteins
C471644:BTRC protein, human; C471643:Btrc protein, mouse; C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin; D044844:beta-Transducin Repeat-Containing Proteins; D019204:GTP-Binding Proteins