Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:B0FTZ7 (catenin)
 18,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The activation of the adenomatous polyposis coli (APC)/beta-catenin/T-cell factor (Tcf) pathway due to beta-catenin gene mutation has been recently implicated in the development of some endometrial carcinomas. beta- and gamma-catenin are structurally and functionally related molecules that participate in cell adhesion and signal transduction. Nuclear accumulation of beta- and gamma-catenin have been related to the activation of the APC/beta-catenin/Tcf pathway. In this study, we investigate the immunohistochemical expression pattern (nuclear vs membranous) of beta- and gamma-catenin in 40 endometrial carcinomas and their correlation with clinicopathological features and microsatellite instability (MI) status. MI was detected at three or more loci in 12 tumors: 11 were endometrioid and one was non-endometrioid. Nuclear catenin expression was found in 13 carcinomas: ten carcinomas had nuclear beta-catenin expression and three carcinomas had nuclear gamma-catenin expression. The nuclear catenin expression pattern significantly correlated with the histological type, International Federation of Gynecology and Obstetrics (FIGO) grade, and the presence of a second neoplasm. Nuclear catenin expression was always observed in low-grade endometrioid carcinomas; it was also more frequently associated with a second carcinoma. No correlation was observed between the catenin expression pattern and the level of myometrial infiltration, stage, associated endometrial hyperplasia, the existence of a source of estrogenic stimulation, and MI. However, four of 13 endometrioid carcinomas in this series had both catenin nuclear expression and MI. These data suggest that at least two different neoplastic pathways can lead to endometrial carcinomas with an endometrioid phenotype. In one, MI would be a key event, while in the other, the APC/beta-catenin/Tcf signaling pathways could be activated. Probably, in some cases, both pathways could simultaneously occur.
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PMID:Beta- and gamma-catenin expression in endometrial carcinoma. Relationship with clinicopathological features and microsatellite instability. 1140 74

Dysfunction of E-cadherin and catenin has been linked to invasiveness and differentiation of tumors. This study aimed to characterize the expression of cadherins and catenins in early gastric carcinoma and their relationship to clinicopathologic characteristics and Helicobacter pylori infection. E-cadherin and alpha-, beta- and gamma-catenins were strongly expressed in normal epithelium but abnormal immunoreactivity of at least one of these four proteins was noted in 48 (90.6%) of 53 early gastric carcinomas. Only 5 cases with intestinal-type tumors had intact expression of E-cadherin and alpha-, beta-, and gamma-catenins. Abnormal immunoreactivity in the tumor tissue was observed in 18 patients (34.0%) for E-cadherin, in 35 (66.0%) for alpha-catenin, in 20 (37.7%) for beta-catenin, and in 37 (69.8%) for gamma-catenin. In diffuse-type tumors, abnormal expression of E-cadherin (60.9 vs. 13.3%, p < 0.0005), alpha-catenin (82.6 vs. 53.3%, p < 0.05) and gamma-catenin (91.3 vs. 53.3%, p < 0.005) was more frequent than in the intestinal type. Ten tumors with lymph node metastasis showed a relatively higher frequency of abnormal expression of E-cadherin (70 vs. 25.6%, p < 0.05) but a lower frequency of abnormal expression of beta-catenin (10 vs. 44.1%, p = 0.07) than those without metastasis. No significant association was found between cadherin/catenin expression and the depth of invasion or the H. pylori status. It was concluded that abnormal expression of E-cadherin and the catenin-mediated cell-cell adhesion system occurs frequently in early gastric carcinogenesis and may play an important role in the genesis of histologic differentiation and in the mode of metastasis of early gastric carcinomas.
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PMID:Immunohistochemical evaluation of cadherin and catenin expression in early gastric carcinomas: correlation with clinicopathologic characteristics and Helicobacter pylori infection. 1140 2

Tumor progression requires the dispersion of epithelial cells from neoplastic clusters and cell invasion of adjacent stromal connective tissue. Aiming at demonstrating the precise relationships between cell dispersion and cell invasion, related respectively to expression of E-cadherin/catenin complex and matrix metalloproteinases (MMPs), we developed an original in vitro model of cell dispersion analysis. Our study reports the validation of this model that allowed us to analyze and quantify the cell cohesion level by means of time-lapse videomicroscopy and computer analysis based on the observation of spatial and temporal cell distribution. Our model was able to distinguish 2 groups among different human bronchial and mammary epithelial cells previously characterized for the expression of E-cadherin/catenin complex and MMPs and their invasive capacity in the Boyden chamber assay. The first group (16HBE14o(-), MCF-7, T47D) that expressed membranous E-cadherin and beta-catenin, and was negative for MMP-2 expression and non-invasive, displayed a highly cohesive pattern corresponding to a cluster spatial distribution. The second group (Beas2B, BZR, BZR-T33, MDA-MB-231, MDA-MB-435, BT549 and HS578T) that was invasive and showed lack of expression of E-cadherin and a cytoplasmic redistribution of beta-catenin, displayed a dispersed pattern corresponding to a random spatial distribution. Downregulation of E-cadherin by a blocking antibody induced a more random distribution. Conversely, expression of E-cadherin by cDNA transfection induced a cluster distribution. Moreover, tumor cell lines that co-expressed MT1-MMP and MMP-2 (Beas2B, BZR, BZR-T33, MDA-MB-435, BT549 and HS578T) showed a more dispersed pattern than tumor cell lines that did not express MMP-2 (MDA-MB-231). In conclusion, we demonstrated that the spatial group behavior of cell lines, i.e., their cohesion/dispersion ability, reflects their invasive properties. Thus, this model of cell dispersion analysis may represent a new test to measure tumor cell aggressiveness.
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PMID:Quantitative cell dispersion analysis: new test to measure tumor cell aggressiveness. 1147 73

It has been well-known that the cadherin-catenin complexes bind with intracellular skeleton actin, which result in stabilization of cellular structure and tissue organization. Therefore, the cadherin-catenin family has been considered prerequisite for normal cell function and the preservation of tissue integrity. In human malignancies especially colon cancers, dysfunction and/or decrease of expression of these proteins have been proposed to prevent differentiation of tumors and to increase invasiveness and poor prognosis. However, recent studies also revealed that a member of this superfamily, beta-catenin, may play an important role in Wnt/wingless intracellular signaling pathway. Decreased expression of this protein or somatic mutation of the beta-catenin gene has been also reported in human carcinomas including various endocrine tumors. Mutant beta-catenin is associated with abnormal nuclear accumulation in tumor cells and subsequently to activate other transcription factors such as Tcf/Lef. This activation eventually results in which upregulation of mRNA and protein levels of various cell growth mediators in these endocrine tumors. Therefore, dysfunction of the cadherin-catenin system is considered to be closely correlated with tumorigenesis and development in human endocrine tumors.
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PMID:The cadherin-catenin superfamily in endocrine tumors. 1147 63

Cell adhesion molecule expression has been linked to disease outcome in prostatic adenocarcinomas (PACs). We evaluated the coordinated expression of catenin-related proteins, E-cadherin, N-cadherin, and CD44s in PACs. Archival sections from 112 PACs were immunostained by an automated method (Ventana Medical Systems, Tucson, AZ) using monoclonal antibodies to alpha- and beta-catenins, p120CTN, E-cadherin, N-cadherin, and CD44s proteins. Immunoreactivity was semiquantitatively scored, and results were evaluated for association between these markers. Staining results were also correlated with tumor grade, stage, ploidy, preoperative serum PSA, and postoperative biochemical disease recurrence. Decreased expression of alpha- and beta- catenins, p120CTN, E-cadherin, and CD44s proteins (range, 5% to 49%) was noted in PACs, and downregulation of each of these proteins correlated with high tumor grade (P =.02 to.0001). Although loss of E-cadherin and p120CTN each correlated with stage (E-cadherin, P =.02; p120CTN, P =.02) and ploidy (E-cadherin, P =.0001; p120CTN, P =.004), downregulation of CD44s correlated with ploidy (P =.002), serum PSA (P =.005), and postoperative disease recurrence (P =.02). N-cadherin was positive in only 5% of PACs and did not correlate with any prognostic parameters. alpha-Catenin downregulation correlated with decreased expression of E-cadherin (P =.0001). Additionally, decreased expression of each of these 2 proteins respectively correlated with loss of beta-catenin (P =.0001 and.004), p120CTN (P =.005 and.001), and CD44s (P =.008 and.01). beta-Catenin expression levels correlated with p120CTN (P =.01). A trend for co-downregulation of CD44s and p120CTN and of CD44s and beta-catenin was observed. In conclusion, the significant association between decreased expression of various members of the CAM family of proteins supports their collective role in mediating cell-cell adhesion. Altered expression of these proteins may be of prognostic value in patients with prostate cancer.
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PMID:Co-downregulation of cell adhesion proteins alpha- and beta-catenins, p120CTN, E-cadherin, and CD44 in prostatic adenocarcinomas. 1152 Dec 30

Transforming growth factor beta1 (TGF-beta1) acts as a tumor suppressor at early stages of carcinogenesis, however, it has also been suggested to promote tumor progression at late stages. To determine at which stage and by what mechanisms this functional switch occurs, we have generated gene-switch-TGF-beta1 mice in which TGF-beta1 transgene expression can be induced in skin tumors at specific stages. These mice were exposed to a chemical carcinogenesis protocol, which allows tumorigenesis to develop in progressive stages from benign papillomas to malignant carcinomas. Remarkably, TGF-beta1 transgene induction in papillomas rapidly induced metastasis. This function is in sharp contrast to its tumor suppressive effect when TGF-beta1 transgene expression was induced early in the protocol. Transgenic papillomas exhibited down-regulation of TGF-beta receptors and their signal transducer, the Smads, and loss of the invasion suppressor E-cadherin/catenin complex in the cell membrane. These molecules were lost only in malignant carcinomas in control mice at a much later stage. Furthermore, transgenic papillomas exhibited elevated expression of matrix metalloproteinases and increased angiogenesis. Our study suggests that TGF-beta1 overexpression may directly induce tumor metastasis by initiating events necessary for invasion. Down-regulation of TGF-beta signaling components in tumor epithelia selectively abolishes growth inhibition, thus, switching the role of TGF-beta1 to a metastasis promoter.
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PMID:Inducible expression of transforming growth factor beta1 in papillomas causes rapid metastasis. 1160 77

To investigate the importance of the microenvironment in bladder cancer invasion, a panel of six bladder carcinoma cell lines (SD, RT112, JON, 1207, T24, and J82) was tested in both in vitro and in vivo invasion assays. Furthermore, invasiveness was correlated with the expression of components of the E-cadherin-catenin complex. The E-cadherin-negative cell lines, T24 and J82, displayed a high in vitro invasive capacity, whereas the E-cadherin-positive cell lines, SD and JON, completely lacked in vitro invasive capacity. In contrast, in vivo invasion was noted for all cell lines, with the exception of cell line JON. Most notably, SD formed highly invasive tumors in vivo. The in vivo invasiveness of the E-cadherin-positive bladder carcinoma cell lines was associated with a heterogeneous expression of the E-cadherin-catenin complex. The discrepancy between in vitro and in vivo invasive behavior implies that, in vivo, the microenvironment plays an important role in the establishment of the invasive phenotype. In addition, it was found that orthotopic xenografting of 1207 and T24 bladder carcinoma cells resulted in site-specific tumor take and an enhanced tumor outgrowth and invasiveness, respectively, compared with heterotopic (i.e., subcutaneous) inoculation. We conclude that the site-specific growth and invasion of the bladder carcinoma cell lines in vivo and the observed assay specific invasion (in vitro vs in vivo) points to an effect of the local (bladder) microenvironment on tumor cell behavior.
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PMID:Influence of the microenvironment on invasiveness of human bladder carcinoma cell lines. 1171 Jun 43

The role of estrogens as one of the prime stimulators of tumor cell proliferation is well recognized; efforts to interfere with the initiation and promotion of breast and other cancers by endocrine manipulation have a long and successful past. The benzothiophene derivate Raloxifene is a relatively recent newcomer into a heterogeneous family of compounds loosely called antiestrogens, which implies their ability to act as antagonists to estrogen effects via competitive binding to various steroid receptors. This is a reductionist explanation, since their action is colorful and varied; they interact with lipid transduction cascades, covalently bind to DNA and to different proteins and regulate growth factors and the expression of various genes, such as erB2, mdr1 and p53; they complex with E-cadherin/catenin and are thus able to induce apoptosis, actively or indirectly. Raloxifene not only modulates estrogen effects, but has been found to reduce bone demineralization and atherogenesis, without carcinogenic stimulation of the endometrium.
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PMID:Raloxifene: another selective estrogen modulator. 1188 29

P120 catenin (p120ctn) belongs to the Armadillo family of proteins, which is implicated in cell-cell adhesion and signal transduction. Owing to alternative splicing and multiple translation initiation codons, several p120ctn isoforms can be expressed from a single gene. All p120ctn isoforms share the central Armadillo repeat domain but have divergent N- and C-termini. Little is known about the biological functions of the different isoforms. In this study, we examined the distribution of various p120ctn isoforms and the consequences of their expression in cultured cells of epidermal origin. Immunohistochemical analysis and western blotting revealed that melanocytes and melanoma cells primarily express the long isoform 1A, whereas keratinocytes express shorter isoforms, especially 3A, which localize to cell-cell adhesion junctions in a calcium-dependent manner. The shortest isoform 4A, which was detected in normal keratinocytes and melanocytes, was generally lost from cells derived from squamous cell carcinomas or melanomas. The C-terminal alternatively spliced exon B was present in the p120ctn transcripts in the colon, intestine and prostate, but was lost in several tumor tissues derived from these organs. To test whether p120ctn isoforms serve in distinct biological functions, we transiently transfected the expression constructs into melanoma cells (1205-Lu) and immortalized keratinocytes (HaCaT). Indeed, distinct domains of p120ctn are responsible for its different biological functions. The prominent branching phenotype was induced equally by isoforms 1A, 2A and 3A, whereas the shortest isoform 4A, which was devoid of the N-terminal domain, completely lacked this ability. Also, the exon-B-encoded sequences, as in the isoform 1AB, were sufficient to abolish the branching phenotype as induced by the isoform 1A. The induction of the branching phenotype cosegregated with the nuclear localization of the p120ctn isoforms 1A, 2A and 3A, whereas the isoforms 4A and 1AB, which were excluded from the nucleus, did not induce the branching phenotype. The N-terminal sequences that contain seven out of eight tyrosine residues, recently characterized as potential candidates for phosphorylation by Src kinase, are required for the nuclear localization and for the formation of the branching phenotype. Finally, expression of the p120ctn isoforms, which caused the branching phenotype, was associated with cellular relocalization of E-cadherin in HaCaT cells. Collectively, we have identified sequences within the p120ctn N-terminus that are prerequisites for both nuclear localization and the p120ctn-induced branching phenotype. Loss of the cytoplasmic pool of p120ctn from tumor cells suggests an important function for such isoforms in normal cells and tissues.
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PMID:Specific sequences in p120ctn determine subcellular distribution of its multiple isoforms involved in cellular adhesion of normal and malignant epithelial cells. 1189 87

beta-Catenin signaling plays a key role in a variety of cellular contexts during embryonic development and tissue differentiation. Aberrant beta-catenin signaling has also been implicated in promoting human colorectal carcinomas as well as a variety of other cancers. To study the molecular and cellular biological functions of beta-catenin in a controlled fashion, we created a regulatable form of activated beta-catenin by fusion to a modified estrogen receptor (ER) ligand binding domain (G525R). Transfection of tissue culture cells with expression vectors encoding this hybrid protein allows the signal transduction function of beta-catenin to be induced by the synthetic estrogen, 4-hydroxytamoxifen, leading to regulated activation of a beta-catenin-lymphocyte enhancer-binding factor-dependent reporter gene as well as induction of endogenous cyclin D1 expression. The activation of ER-beta-catenin signaling rescues RK3E cells from anoikis and correlates with an increased phosphorylation of mitogen-activated protein kinase. The inhibition of anoikis by ER-beta-catenin can be abolished by a mitogen-activated protein kinase pathway inhibitor, PD98059. Evidence is also provided to show that ER-beta-catenin down-regulates cadherin protein levels. These findings support a key role for activated beta-catenin signaling in processes that contribute to tumor formation and progression.
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PMID:Protection against anoikis and down-regulation of cadherin expression by a regulatable beta-catenin protein. 1190 89


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