scholarly journals Corepressor CtBP and Nuclear Speckle Protein Pnn/DRS Differentially Modulate Transcription and Splicing of the E-Cadherin Gene

2007 ◽  
Vol 28 (5) ◽  
pp. 1584-1595 ◽  
Author(s):  
Roman Alpatov ◽  
Yujiang Shi ◽  
Gustavo C. Munguba ◽  
Babak Moghimi ◽  
Jeong-Hoon Joo ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Molecular Switches ◽  
Suppressor Gene ◽  
Mrna Processing ◽  
Mrna Splicing ◽  
Gene Promoters ◽  
Nuclear Speckle ◽  
Tumorigenic Potential ◽  
E Cadherin

ABSTRACT CtBP is a transcriptional corepressor with tumorigenic potential that targets the promoter of the tumor suppressor gene E-cadherin. Pnn/DRS (Pnn) is a “nuclear speckle”-associated protein involved in mRNA processing as well as transcriptional regulation of E-cadherin via its binding to CtBP. Here, we show that CtBP can recruit Pnn to CtBP-associated complexes, resulting in Pnn-dependent chromatin remodeling at the E-cadherin promoter. In addition, CtBP and Pnn can differentially modulate E-cadherin mRNA splicing, with polymerase II serving as an interface in this event. Therefore, the Pnn/CtBP functional interplay represents a novel mechanism linking the corepressor CtBP and Pnn to the transcription-coupled mRNA splicing of a major tumor suppressor gene. Our findings implicate the existence of the molecular switches involved in tumorigenesis, which coordinate promoter-specific events and mRNA processing, by serving as bridging elements between the regulatory complexes both at gene promoters and within the mRNA splicing machineries.

scholarly journals Functional evidence for a second tumor suppressor gene on human chromosome 17

1994 ◽  
Vol 14 (1) ◽  
pp. 534-542
Author(s):  
P Chen ◽  
N Ellmore ◽  
B E Weissman
Keyword(s):  
Tumor Suppressor ◽  
Cell Line ◽  
Tumor Suppressor Gene ◽  
Cell Lines ◽  
Suppressor Gene ◽  
Chromosome 17 ◽  
Hybrid Cells ◽  
Tumorigenic Potential ◽  
Normal Human ◽  
Second Tumor

The development and progression of human tumors often involves inactivation of tumor suppressor gene function. Observations that specific chromosome deletions correlate with distinct groups of cancer suggest that some types of tumors may share common defective tumor suppressor genes. In support of this notion, our initial studies showed that four human carcinoma cell lines belong to the same complementation group for tumorigenic potential. In this investigation, we have extended these studies to six human soft tissue sarcoma cell lines. Our data showed that hybrid cells between a peripheral neuroepithelioma (PNET) cell line and normal human fibroblasts or HeLa cells were nontumorigenic. However, hybrid cells between the PNET cell line and five other soft tissue sarcoma cell lines remained highly tumorigenic, suggesting at least one common genetic defect in the control of tumorigenic potential in these cells. To determine the location of this common tumor suppressor gene, we examined biochemical and molecular polymorphic markers in matched pairs of tumorigenic and nontumorigenic hybrid cells between the PNET cell line and a normal human fibroblast. The data showed that loss of the fibroblast-derived chromosome 17 correlated with the conversion from nontumorigenic to tumorigenic cells. Transfer of two different chromosome 17s containing a mutant form of the p53 gene into the PNET cell line caused suppression of tumorigenic potential, implying the presence of a second tumor suppressor gene on chromosome 17.

scholarly journals Quantitative Methylation Profiles for Multiple Tumor Suppressor Gene Promoters in Salivary Gland Tumors

PLoS ONE ◽  
2010 ◽  
Vol 5 (5) ◽  
pp. e10828 ◽  
Author(s):  
Megan L. Durr ◽  
Wojciech K. Mydlarz ◽  
Chunbo Shao ◽  
Marianna L. Zahurak ◽  
Alice Y. Chuang ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Suppressor Gene ◽  
Salivary Gland Tumors ◽  
Gene Promoters ◽  
Multiple Tumor

Aberrant Splicing of the E-Cadherin Gene Is a Novel Mechanism of Gene Silencing in Chronic Lymphocytic Leukemia Cells

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2842-2842
Author(s):  
Sanjai Sharma ◽  
Alan Lichtenstein
Keyword(s):  
B Cells ◽  
Chronic Lymphocytic Leukemia ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Real Time Pcr ◽  
Exon Skipping ◽  
Suppressor Gene ◽  
Lymphocytic Leukemia ◽  
Exon 11 ◽  
E Cadherin

Abstract Premature termination codons (PTCs) in tumor suppressor genes can contribute to oncogenesis. PTCs prematurely terminate transcription, leading to expression of a truncated, mRNA. The nonsense-mediated degradation (NMD) pathway degrades the aberrant transcripts resulting in loss of expression. To identify RNA transcripts with PTCs in chronic lymphocytic leukemia specimens (CLL), we employed a microarray technique to screen for genes which upregulate their RNA signal upon NMD blockade. In the list of genes with highest upregulation, we identified the E-cadherin gene, a known tumor suppressor gene. On further investigation, we found that the PTC was due to stabilization of an alternatively spliced E-cadherin transcript. This transcript completely lacks exon 11 (exon skipping), resulting in a frameshift and a PTC which is recognized by the NMD pathway and degraded. RT-PCR analysis demonstrated that the exon 11 skipping occurs in normal B cells as well but at a much lower frequency. A real time PCR based strategy to quantify the relative amount of spliced transcript confirmed a 10–30 fold increase in exon 11 skipping in CLL cells (n=29) as compared to normal B cells (n=4) and the degree of skipping increased with increased Rai stage. In addition, real time PCR also demonstrated a significant decrease in total wild type E-cadherin RNA expression in 58% of CLL specimens compared to normal B cells. As prior work demonstrates an upregulated wnt/β-catenin pathway in CLL and, and that E-cadherin can be a physiologic regulator of this pathway, we tested wnt pathway reporter expression in CLL specimens. High expression was identified and ectopic expression of E-cadherin in some samples with E-cadherin loss was sufficient to inhibit the wnt-reporter activity. This suggests that E-cadherin loss, possibly due to exon 11 alternative splicing and exon skipping plays a role in upregulated wnt signaling. As there are no mutations in exon 11 or its flanking intronic regions in CLL cells, our results suggest a novel mechanism of E-cadherin gene inactivation in which the trans-factors/splicing factors in malignant B lymphocytes induce an increased nonproductive splicing of a tumor suppressor gene.

scholarly journals Mechanisms of inactivation of E-cadherin in breast carcinoma: modification of the two-hit hypothesis of tumor suppressor gene

Oncogene ◽  
2001 ◽  
Vol 20 (29) ◽  
pp. 3814-3823 ◽  
Author(s):  
Chun-Wen Cheng ◽  
Pei-Ei Wu ◽  
Jyh-Cherng Yu ◽  
Chiun-Sheng Huang ◽  
Chung-Tai Yue ◽  
...  
Keyword(s):  
Breast Carcinoma ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Suppressor Gene ◽  
E Cadherin

Oncoprotein profiles of primary peritoneal malignant mixed müllerian tumors

2003 ◽  
Vol 13 (6) ◽  
pp. 870-874
Author(s):  
J. S. Ng ◽  
A. C. Han ◽  
M. I. Edelson ◽  
N. G. Rosenblum
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Antigen Expression ◽  
Suppressor Gene ◽  
Rare Tumor ◽  
Membrane Expression ◽  
P53 Overexpression ◽  
Classical Cadherins ◽  
E Cadherin

Primary peritoneal malignant mixed müllerian tumors (MMMTs) are extremely rare and highly aggressive malignancies associated with poor clinical prognoses. We present a clinicopathologic review of three cases of this rare tumor by examining expression of selected oncoproteins by immunohistochemistry. Three consecutive cases of primary peritoneal MMMT were examined by paraffin immunohistochemistry for expression of p53, p16, BCL2, CerbB2, and classical cadherins E-cadherin, P-cadherin, and N-cadherin. All three cases expressed p16, but showed less consistent expression of other markers, with one case expressing p53 and one expressing BCL2. All cases were negative for membrane expression of Cerb-B2. The three classical cadherins were expressed in two cases with one case showing only weak N- and P-cadherin expression. No difference in antigen expression was seen in the epithelial compared to sarcomatous components. We conclude that p16 may be a common tumor suppressor gene expressed in peritoneal MMMT. P53 overexpression may be of lesser frequency in peritoneal MMMT compared to MMMT from the ovary and the uterus. We did not observe any difference in antigen expression between areas of epithelial or sarcomatous differentiation, which would support a single pluripotential malignant clone in the histogenesis of these tumors.

scholarly journals Functional evidence for a second tumor suppressor gene on human chromosome 17.

1994 ◽  
Vol 14 (1) ◽  
pp. 534-542 ◽  
Author(s):  
P Chen ◽  
N Ellmore ◽  
B E Weissman
Keyword(s):  
Tumor Suppressor ◽  
Cell Line ◽  
Tumor Suppressor Gene ◽  
Cell Lines ◽  
Suppressor Gene ◽  
Chromosome 17 ◽  
Hybrid Cells ◽  
Tumorigenic Potential ◽  
Normal Human ◽  
Second Tumor

The development and progression of human tumors often involves inactivation of tumor suppressor gene function. Observations that specific chromosome deletions correlate with distinct groups of cancer suggest that some types of tumors may share common defective tumor suppressor genes. In support of this notion, our initial studies showed that four human carcinoma cell lines belong to the same complementation group for tumorigenic potential. In this investigation, we have extended these studies to six human soft tissue sarcoma cell lines. Our data showed that hybrid cells between a peripheral neuroepithelioma (PNET) cell line and normal human fibroblasts or HeLa cells were nontumorigenic. However, hybrid cells between the PNET cell line and five other soft tissue sarcoma cell lines remained highly tumorigenic, suggesting at least one common genetic defect in the control of tumorigenic potential in these cells. To determine the location of this common tumor suppressor gene, we examined biochemical and molecular polymorphic markers in matched pairs of tumorigenic and nontumorigenic hybrid cells between the PNET cell line and a normal human fibroblast. The data showed that loss of the fibroblast-derived chromosome 17 correlated with the conversion from nontumorigenic to tumorigenic cells. Transfer of two different chromosome 17s containing a mutant form of the p53 gene into the PNET cell line caused suppression of tumorigenic potential, implying the presence of a second tumor suppressor gene on chromosome 17.

scholarly journals E-cadherin and APC compete for the interaction with beta-catenin and the cytoskeleton.

1994 ◽  
Vol 127 (6) ◽  
pp. 2061-2069 ◽  
Author(s):  
J Hülsken ◽  
W Birchmeier ◽  
J Behrens
Keyword(s):  
Cell Adhesion ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Gene Product ◽  
Suppressor Gene ◽  
Cell Junctions ◽  
Beta Catenin ◽  
Tumor Suppressor Gene Product ◽  
Product Forms ◽  
E Cadherin

beta-Catenin is involved in the formation of adherens junctions of mammalian epithelia. It interacts with the cell adhesion molecule E-cadherin and also with the tumor suppressor gene product APC, and the Drosophila homologue of beta-catenin, armadillo, mediates morphogenetic signals. We demonstrate here that E-cadherin and APC directly compete for binding to the internal, armadillo-like repeats of beta-catenin; the NH2-terminal domain of beta-catenin mediates the interaction of the alternative E-cadherin and APC complexes to the cytoskeleton by binding to alpha-catenin. Plakoglobin (gamma-catenin), which is structurally related to beta-catenin, mediates identical interactions. We thus show that the APC tumor suppressor gene product forms strikingly similar associations as found in cell junctions and suggest that beta-catenin and plakoglobin are central regulators of cell adhesion, cytoskeletal interaction, and tumor suppression.

Abstract 4929: Hypermethylation of tumor suppressor gene promoters in basal cell carcinoma

2010 ◽  
Author(s):  
Tjinta Brinkhuizen ◽  
Manon van Engeland ◽  
Ariënne van Marion ◽  
Maurice van Steensel
Keyword(s):  
Tumor Suppressor ◽  
Basal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Tumor Suppressor Gene ◽  
Basal Cell ◽  
Suppressor Gene ◽  
Gene Promoters

scholarly journals Methylation pattern of tumor-suppressor gene promoters as putative noninvasive diagnostic markers for prostate cancer

2021 ◽  
Vol 37 (1) ◽  
pp. 23-32
Author(s):  
O. S. Mankovska ◽  
A. S. Korsakova ◽  
K. R. Cherniavskyi ◽  
O. A. Kononenko ◽  
E. O. Stakhovskyy ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Suppressor Gene ◽  
Methylation Pattern ◽  
Diagnostic Markers ◽  
Gene Promoters

scholarly journals Over-expression of Hsp83 in grossly depleted hsrω lncRNA background causes synthetic lethality and l(2)gl phenocopy in Drosophila

2018 ◽  
Author(s):  
Mukulika Ray ◽  
Sundaram Acharya ◽  
Sakshi Shambhavi ◽  
Subhash C. Lakhotia
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Rna Sequencing ◽  
Synthetic Lethality ◽  
Suppressor Gene ◽  
Gene Promoters ◽  
Larval Life ◽  
Over Expression ◽  
Regulatory Circuits ◽  
Omega Speckles

AbstractWe examined interactions between Hsp83 and hsrω lncRNAs in hsrω66Hsp90GFP homozygotes, which almost completely lack hsrω lncRNAs but over-express Hsp83. All +/+; hsrω66Hsp90GFP progeny died before third instar. Rare Sp/CyO; hsrω66Hsp90GFP reached third instar stage but phenocopied l(2)gl mutants, dying after prolonged larval life, becoming progressively bulbous and transparent with enlarged brain. Additionally, ventral ganglia were elongated. However, hsrω66Hsp90GFP/TM6B heterozygotes, carrying +/+ or Sp/CyO second chromosomes, developed normally. Total RNA sequencing (+/+, +/+; hsrω66/hsrω66, Sp/CyO; hsrω66/hsrω66, +/+; Hsp90GFP/Hsp90GFP, and Sp/CyO; hsrω66Hsp90GFP/hsrω66Hsp90GFP late third instar larvae) revealed similar effects on many genes in hsrω66 and Hsp90GFP homozygotes. Besides additive effect on many of them, numerous additional genes were affected in Sp/CyO; hsrω66Hsp90GFP larvae, with l(2)gl and several genes regulating CNS being highly down-regulated in surviving Sp/CyO; hsrω66Hsp90GFP larvae, but not in hsrω66 or Hsp90GFP single mutants. Hsp83 binds at these gene promoters. Several omega speckle associated hnRNPs too may bind with these genes and transcripts. Hsp83-hnRNP interactions are also known. Thus, elevated Hsp83 in altered hnRNP distribution and dynamics, following absence of hsrω lncRNAs and omega speckles, background can severely perturb regulatory circuits with unexpected consequences, including down-regulation of tumor suppressor gene like l(2)gl.

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