CLCA2 tumour suppressor gene in 1p31 is epigenetically regulated in breast cancer

Li, Xiurong; Cowell, John K.; Sossey‐Alaoui, Khalid

doi:10.1038/sj.onc.1207249

Cited by 55 publications

(51 citation statements)

References 33 publications

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“…The relationship between loss of hCLCA2 expression and tumorigenicity has been confirmed, providing evidence that hCLCA2 is the product of the hitherto unidentified 1p31 breast cancer tumor suppressor gene (112). The importance of the 1p31 locus is illustrated by the loss of heterozygosity in this region in 60% of breast tumors (87).…”

Section: Loss Of Clca In Tumorigenic Cell Linesmentioning

confidence: 78%

“…CLCA functions as a tumor suppressor within the transformed cell, possibly by modulating ion transport. Expression of CLCA protein is frequently lost in tumor cell lines (49,79,112). However, tumor cells that have lost CLCA expression can bind endothelial-expressed CLCA via a novel endothelial CLCA/␤ 4 -integrin interaction.…”

Section: A Cell Cycle Controlmentioning

confidence: 99%

“…However, another original CLCA protein, LuECAM-1, functions in tumor cell adhesion and metastasis (1)(2)(3)50). This role for LuECAM-1 in tumor adhesion appears to conflict with significant tumor suppressor activity reported for other CLCA proteins (49,79,112). CLCA proteins have also been connected recently to the regulation of mucus production in the asthmatic airway (88, 135), and to ion transport in the airway of cystic fibrosis patients (83, 84).…”

Section: Introduction To Clca Proteinsmentioning

confidence: 99%

“…Hypermethylation of the hCLCA2 promoter may cause this transcriptional downregulation in tumorigenic cell lines, inviting speculation that hCLCA2 is the 1p31 breast cancer tumor suppressor gene (112). mCLCA1 is also normally expressed in mammary tissue, and mCLCA1 transcripts were not found in tumor cells, suggesting disrupted expression at the promoter level in the tumor (49,112). Abnormal RNA processing may also disrupt CLCA2 expression (79, 112).…”

Section: Loss Of Clca In Tumorigenic Cell Linesmentioning

confidence: 99%

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Structure and Function of CLCA Proteins

Loewen¹,

Forsyth²

2005

Physiological Reviews

121

126

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CLCA proteins were discovered in bovine trachea and named for a calcium-dependent chloride conductance found in trachea and in other secretory epithelial tissues. At least four closely located gene loci in the mouse and the human code for independent isoforms of CLCA proteins. Full-length CLCA proteins have an unprocessed mass ratio of ∼100 kDa. Three of the four human loci code for the synthesis of membrane-associated proteins. CLCA proteins affect chloride conductance, epithelial secretion, cell-cell adhesion, apoptosis, cell cycle control, mucus production in asthma, and blood pressure. There is a structural and probable functional divergence between CLCA isoforms containing or not containing β4-integrin binding domains. Cell cycle control and tumor metastasis are affected by isoforms with the binding domains. These isoforms are expressed prominently in smooth muscle, in some endothelial cells, in the central nervous system, and also in secretory epithelial cells. The isoform with disrupted β4-integrin binding (hCLCA1, pCLCA1, mCLCA3) alters epithelial mucus secretion and ion transport processes. It is preferentially expressed in secretory epithelial tissues including trachea and small intestine. Chloride conductance is affected by the expression of several CLCA proteins. However, the dependence of the resulting electrical signature on the expression system rather than the CLCA protein suggests that these proteins are not independent Ca2+-dependent chloride channels, but may contribute to the activity of chloride channels formed by, or in conjunction with, other proteins.

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Section: Loss Of Clca In Tumorigenic Cell Linesmentioning

confidence: 78%

Section: A Cell Cycle Controlmentioning

confidence: 99%

Section: Introduction To Clca Proteinsmentioning

confidence: 99%

Section: Loss Of Clca In Tumorigenic Cell Linesmentioning

confidence: 99%

See 2 more Smart Citations

Structure and Function of CLCA Proteins

Loewen¹,

Forsyth²

2005

Physiological Reviews

121

126

View full text Add to dashboard Cite

show abstract

“…Among these, CLCA2 (chloride channel accessory 2) was identified as the most upregulated transcript upon Fra-1 and c-Jun knockdown. Interestingly, reduced expression of CLCA2 was frequently observed in breast cancer (26). In addition, CLCA2 was shown to play a crucial role in inhibition of cancer cell migration and invasion (27,28).…”

Section: Fra-1 and C-jun Common Target Genes Regulating Cell Prolifermentioning

confidence: 99%

Genome-wide Profiling of AP-1–Regulated Transcription Provides Insights into the Invasiveness of Triple-Negative Breast Cancer

et al. 2014

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Triple-negative breast cancer (TNBC) is an aggressive clinical subtype accounting for up to 20% of all breast cancers, but its malignant determinants remain largely undefined. Here, we show that in TNBC the overexpression of Fra-1, a component of the transcription factor AP-1, offers prognostic potential. Fra-1 depletion or its heterodimeric partner c-Jun inhibits the proliferative and invasive phenotypes of TNBC cells in vitro. Similarly, RNAi-mediated attenuation of Fra-1 or c-Jun reduced cellular invasion in vivo in a zebrafish tumor xenograft model. Exploring the AP-1 cistrome and the AP-1-regulated transcriptome, we obtained insights into the transcriptional regulatory networks of AP-1 in TNBC cells. Among the direct targets identified for Fra-1/c-Jun involved in proliferation, adhesion, and cell-cell contact, we found that AP-1 repressed the expression of E-cadherin by transcriptional upregulation of ZEB2 to stimulate cell invasion. Overall, this work illuminates the pathways through which TNBC cells acquire invasive and proliferative properties. Cancer Res; 74(14); 3983-94. Ó2014 AACR.

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Quantitative microsatellite analysis to delineate the commonly deleted region 1p22.3 in mantle cell lymphomas

Balakrishnan

Neuhoff

Rudolph

et al. 2006

Genes Chromosomes & Cancer

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The molecular pathogenesis of mantle cell lymphomas (MCL), a subset of B-cell non-Hodgkin's lymphomas with a poor prognosis, is still poorly understood. In addition to the characteristic primary genetic alteration t(11;14)(q13;q32), several further genetic changes are present in most cases. One of the most frequent genomic imbalances is the deletion of 1p22.1-p31.1 observed in nearly one-third of MCL cases. This might indicate the presence of tumor suppressor gene(s) in this critical region of deletion. Quantitative microsatellite analysis (QuMA) is a real-time PCR-based method to detect DNA copy number changes. Since QuMA has the resolving power to detect subtle genomic alterations, including homozygous deletions, this may help to identify candidate tumor suppressor genes from deleted regions. To gain more insight into the molecular pathogenesis of MCL, QuMA was performed on genomic DNA from 57 MCL cases. Eight microsatellite loci mapping to the chromosomal region 1p22.3 were analyzed. Losses were observed in 51 of the 57 ( approximately 89.5%) samples. Two cases showed a homozygous deletion at the locus containing the gene SH3GLB1, which plays a key role in Bax-mediated apoptosis. Two hotspots with copy number losses were detected at chromosomal localizations 85.4 and 86.6 Mb encompassing BCL10 and CLCA2. Both the genes seem to be attractive candidates to study tumor suppressor function in MCL.

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CLCA2 tumour suppressor gene in 1p31 is epigenetically regulated in breast cancer

Cited by 55 publications

References 33 publications

Structure and Function of CLCA Proteins

Structure and Function of CLCA Proteins

Genome-wide Profiling of AP-1–Regulated Transcription Provides Insights into the Invasiveness of Triple-Negative Breast Cancer

Quantitative microsatellite analysis to delineate the commonly deleted region 1p22.3 in mantle cell lymphomas

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