A.V. Gerstein and T.A. Almeida contributed equally to this work.
APC/CTNNB1 (β-catenin) pathway alterations in human prostate cancers
Article first published online: 1 FEB 2002
Copyright © 2002 Wiley-Liss, Inc.
Genes, Chromosomes and Cancer
Volume 34, Issue 1, pages 9–16, May 2002
How to Cite
Gerstein, A. V., Almeida, T. A., Zhao, G., Chess, E., Shih, I.-M., Buhler, K., Pienta, K., Rubin, M. A., Vessella, R. and Papadopoulos, N. (2002), APC/CTNNB1 (β-catenin) pathway alterations in human prostate cancers. Genes Chromosom. Cancer, 34: 9–16. doi: 10.1002/gcc.10037
- Issue published online: 18 MAR 2002
- Article first published online: 1 FEB 2002
- Manuscript Accepted: 9 AUG 2001
- Manuscript Received: 27 JUN 2001
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. © 2002 Wiley-Liss, Inc.