title: Detection and analysis of beta-catenin mutations in prostate cancer.
abstract: BACKGROUND
  E-cadherin and alpha-catenin are components of adherens junctions which mediate calcium-dependent, cell-cell adhesion in a homotypic manner. Both these molecules have been defined as useful tumor markers as their altered expression correlates with increased tumor aggressiveness and dedifferentiation. More recently, alterations of a third component of adherens junctions, beta-catenin, have been observed to play a role in several human cancers. Dysregulation of beta-catenin, either by direct mutation or by defects in interacting pathways/regulators, can result in its cytoplasmic accumulation and nuclear translocation. In the nucleus, beta-catenin forms a transcriptional complex capable of upregulating target genes, many of which encode proliferative factors. Given its oncogenic activity and connection to human cancer, we examined the beta-catenin gene and its expression in prostate cancer.
  
  
  METHODS
  By single-stranded conformational polymorphism (SSCP) and DNA sequencing analyses, we screened exon 3 of beta-catenin from a panel of 81 primary tumors obtained at radical prostatectomy, 22 lymph node metastases from untreated patients, and a unique set of 61 metastatic tissues from 19 patients who died of hormone-refractory disease.
  
  
  RESULTS
  We found putative activating mutations (missense and deletion) at a rate of 5% (7/138). One patient had the same 72 base pair deletion in each of nine separate metastases examined, indicating that this change was associated with a clonal population of metastatic cells.
  
  
  CONCLUSIONS
  Immunohistological staining of mutation-positive tumors demonstrated beta-catenin accumulation and nuclear localization in a heterogeneous fashion. Consistent with this in vivo finding, our in vitro analyses demonstrate that certain mutations can result in increased beta-catenin nuclear activity in prostate cancer cell lines. These data implicate the beta-catenin signaling pathway in the development of a subset of prostate cancers.
authors: Brady Urological Institute, Research Laboratories, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA.
authors: D R
authors: DR
authors: Chesire
authors: C M
authors: CM
authors: Ewing
authors: J
authors: J
authors: Sauvageot
authors: G S
authors: GS
authors: Bova
authors: W B
authors: WB
authors: Isaacs
mesh_terms: D000818:Animals; D003598:Cytoskeletal Proteins / Q000096:biosynthesis / Q000235:genetics*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D005091:Exons; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008856:Microscopy, Fluorescence; D020125:Mutation, Missense; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D018807:Polymorphism, Single-Stranded Conformational; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017384:Sequence Deletion; D015534:Trans-Activators; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D051176:beta Catenin
chemical_list: C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D004273:DNA, Neoplasm; D015534:Trans-Activators; D051176:beta Catenin