1500

CTNND1

CAS|CTNND|P120CAS|P120CTN|p120|p120(CAS)|p120(CTN);catenin (cadherin-associated protein), delta 1;CTNND1;catenin (cadherin-associated protein), delta 1

cadherin-associated Src substrate|catenin delta-1|p120 catenin

11q11

protein-coding

Count: 2; Pubmed_search,Generif

p120-catenin (p120ctn) interacts with E-cadherin, but to our knowledge, no formal proof that p120ctn functions as a bona fide tumor suppressor gene has emerged to date. We report herein that p120ctn loss leads to tumor development in mice. We have generated a conditional knockout model of p120ctn whereby mice develop preneoplastic and neoplastic lesions in the oral cavity, esophagus, and squamous forestomach. Tumor-derived cells secrete granulocyte macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF), monocyte chemotactic protein-1 (MCP-1), and tumor necrosis factor-alpha (TNFalpha). The tumors contain significant desmoplasia and immune cell infiltration. Immature myeloid cells comprise a significant percentage of the immune cells present and likely participate in fostering a favorable tumor microenvironment, including the activation of fibroblasts.CI - Copyright (c) 2011 Elsevier Inc. All rights reserved.

Tumor progression in epithelial tissues is characterized by a series of genetic and epigenetic changes that lead ultimately to metastasis. Alterations in E-cadherin and its cytoplasmic regulators, the catenins, have been implicated as central to this process. Here, we focus on p120-catenin and its rising incidence in the pathology literature as a molecule altered in human tumors. The data show that p120 is frequently altered and/or lost in tumors of the colon, bladder, stomach, breast, prostate, lung, and pancreas. Moreover, in some cases p120 loss appears to be an early event in tumor progression, possibly preceding loss of E-cadherin. Potential roles of p120 as a tumor suppressor or metastasis promoter are discussed.

Radiation-induced acute myeloid leukemias (AMLs) in the mouse are characterized by chromosome 2 deletions. Previous studies showed that a minimal deleted region (mdr) of approximately 6.5 cM is lost from one homologue in chromosome 2-deleted AMLs. An AML tumor suppressor gene is proposed to map within this mdr. In this study, we refine the mdr to a I cM interval between markers D2Mit126 and D2Mit185 by microsatellite analysis of 21 primary radiation-induced F I AMLs. The construction of a partial yeast artificial chromosome (YAC) contig spanning the mdr and the location of six known genes indicated that the 1 cM mdr is homologous to human 11p11-12, a region implicated in some human AMLs. Screening of five cell lines derived from primary radiation-induced AMLs for homozygous loss of microsatellites and genes mapping within the mdr revealed loss of both copies of the hemopoietic tissue-specific transcription factor Sfpi1(PU.1/Spi1) in one cell line. Studies of primary and F1 AMLs failed to implicate Sfpi1 as the AML tumor suppressor gene. YAC contig construction, together with data suggesting that the critical gene flanks Sfpi1, represents significant progress toward identifying an AML tumor suppressor gene.