Claudin 1 in Breast Tumorigenesis: Revelation of a Possible Novel “Claudin High” Subset of Breast Cancers

Myal, Yvonne; Leygue, Etienne; Blanchard, Anne

doi:10.1155/2010/956897

Cited by 71 publications

(69 citation statements)

References 74 publications

(114 reference statements)

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“…The increase in Cldn1 expression induced by V in mammary glands is consistent with the modulation of expression of this gene by androgens previously reported in mouse immature Sertoli cells (Gye 2003). Changes in the expression of the gene encoding claudin 1 (Cldn1), the major component of the epithelial tight junctions, have also been reported to be associated with tumorigenesis in human breast (Myal et al 2010). We observed, for the first time, the presence of KRT17 in myoepithelial cells (Fig.…”

Section: Discussionsupporting

confidence: 90%

In utero and lactational exposure to vinclozolin and genistein induces genomic changes in the rat mammary gland

Saad

Toullec

Vacher

et al. 2012

Journal of Endocrinology

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Exposure to low doses of environmental estrogens such as bisphenol A and genistein (G) alters mammary gland development. The effects of environmental anti-androgens, such as the fungicide vinclozolin (V), on mammary gland morphogenesis are unknown. We previously reported that perinatal exposure to G, V, and the GV combination causes histological changes in the mammary gland during the peripubertal period, suggesting alterations to the peripubertal hormone response. We now investigate whether perinatal exposure to these compounds alters the gene expression profiles of the developing glands to identify the dysregulated signaling pathways and the underlying mechanisms. G, V, or GV (1 mg/kg body weight per day) was added to diet of Wistar rats, from conception to weaning; female offspring mammary glands were collected at postnatal days (PNDs) 35 and 50. Genes displaying differential expression and belonging to different functional categories were validated by quantitative PCR and immunocytochemistry. At PND35, G had little effect; the slight changes noted were in genes related to morphogenesis. The changes following exposure to V concerned the functional categories associated with development (Cldn1, Krt17, and Sprr1a), carbohydrate metabolism, and steroidogenesis. The GV mixture upregulated genes (Krt17, Pvalb, and Tnni2) involved in muscle development, indicating effects on myoepithelial cells during mammary gland morphogenesis. Importantly, at PND50, cycling females exposed to GV showed an increase in the expression of genes (Csn2, Wap, and Elf5) related to differentiation, consistent with the previously reported abnormal lobuloalveolar development previously described. Thus, perinatal exposure to GV alters the mammary gland hormone response differently at PND35 (puberty) and in animals with established cycles.

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Section: Discussionsupporting

confidence: 90%

In utero and lactational exposure to vinclozolin and genistein induces genomic changes in the rat mammary gland

Saad

Toullec

Vacher

et al. 2012

Journal of Endocrinology

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“…The complexity of CLDN1 was proposed because its dual role as a tumor suppressor and promoter, as well as a positive and negative prognostic factor in different cancers, including breast (10,11), gastric (12), ovarian (13), lung (14) and colon (15)(16)(17). Decreased expression of CLDN1 is correlated with recurrence status in breast cancer (18).…”

Section: Introductionmentioning

confidence: 99%

The expression of Claudin 1 correlates with β-catenin and is a prognostic factor of poor outcome in gastric cancer

Huang

et al. 2014

International Journal of Oncology

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Abstract. Claudin 1 is one of the tight junction proteins, which are critical in the maintenance of epithelial integrity. Aberrant regulation of CLDN1 and its correlation with β-catenin have been discovered in malignant tumors. The present study aimed to investigate the expression profile and clinical relevance of CLDN1 and β-catenin. The protein levels of CLDN1 and β-catenin were examined using immunohistochemical staining. The characteristics of expression profile and prognostic value were analyzed using Pearson's χ 2 test and Kaplan-Meier analysis, respectively. β-catenin overexpression and knockdown were used to investigate its role in regulating CLDN1 expression. We showed that CLDN1 was overexpressed in intestinal-type, presence of lymph node metastasis, higher TNM stage in gastric cancer patients and correlated with decreased overall survival. The characteristics of CLDN1 expression were associated with that of β-catenin. CLDN1 and β-catenin showed similar prognostic value in intestinal-type gastric cancers. β-catenin knockdown and overexpression in cell models revealed a positive relation between CLDN1 and β-catenin. Our study demonstrated that CLDN1 is a biomarker for intestinal-type gastric cancer with shorter survival. The expression of CLDN1 was strongly associated with β-catenin in gastric cancer patients and a gastric cancer cell model. IntroductionGastric cancer is the fourth most common cancer worldwide and is the second most common cause of cancer-related deaths.Gastric cancer has a poor prognosis (1). Although the 5-year survival rate in patients with early-stage disease is ~90%, since the vast majority present with distant metastasis, the overall 5-year survival rate is typically <20% (2). The 5-year survival rate has also been significantly correlated with the degree of tumor invasion, the presence of lymph node and/ or distant metastases and the TNM stage (3,4). However, very limited number of molecules that have clinicopathological significance in gastric cancer has been discovered.Claudin 1 (CLDN1) is one of the integral membrane proteins that constitute tight junctions. Tight junctions are essential for the tight sealing of cellular sheets and maintaining homeostasis (5). Absence of tight junctions or defective tight junctions is associated with the development of the neoplastic phenotype in epithelial cells (6). Thus it is accepted that the disruption of tight junctions leads to loss of cohesion, invasiveness and the lack of differentiation, thereby promoting tumorigenesis. CLDN1 is found to regulate intestinal epithelial homeostasis through the modulation of Notch-signaling (7). Many chemicals and nutrition can regulate CLDN1 expression through different pathways (8,9) to maintain the integrity of intestinal barrier function.The complexity of CLDN1 was proposed because its dual role as a tumor suppressor and promoter, as well as a positive and negative prognostic factor in different cancers, including breast (10,11), gastric (12), ovarian (13), lung (14) and colon (15-17). Decreased exp...

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“…Downregulation of claudin-1 is intimately associated with tumorigenesis in breast (13,14), prostate (15) and melanocytic neoplasia (16). It is postulated that the impact of claudin-1 on cancer invasion and metastasis is through its regulation of certain invasion/metastasis suppressors or enhancers (17,18). As significant loss of claudin-1 expression and overexpression of DEC1 are commonly observed in the progression of various types of cancers including breast cancer, we aimed to ascertain whether DEC1 modulates breast cancer invasion through its regulation of claudin-1.…”

Section: Introductionmentioning

confidence: 99%

DEC1 is positively associated with the malignant phenotype of invasive breast cancers and negatively correlated with the expression of claudin-1

Liu

Miao

Wang

et al. 2013

International Journal of Molecular Medicine

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Abstract. Differentiated embryo-chondrocyte expressed gene 1 (DEC1) is a basic helix-loop-helix transcriptional regulator, reportedly involved in cell growth, differentiation, apoptosis and tumorigenesis. In breast cancer, DEC1 expression correlates with increased malignant potential and invasiveness. Nevertheless, the detailed mechanisms by which DEC1 modulates breast cancer progression are still unclear. Claudin-1, an important tight junction protein, functions as a tumor invasion suppressor. In the present study, the relationship between DEC1 and claudin-1 in 147 cases of invasive breast ductal carcinomas was examined by immunohistochemistry. Based on the data, DEC1 expression was elevated in invasive breast ductal carcinomas and DEC1 levels were positively correlated with tumor grade (P=0.023). Moreover, DEC1 expression was negatively correlated with the claudin-1 level (correlation coefficient =-0.245, P=0.003). We further identified that, in MCF-7 and MDA-MB-231 breast cancer cell lines, DEC1 knockdown led to the enhanced expression of claudin-1 at both the mRNA and protein levels, and reduced cell invasive capacity. Collectively, our data suggest that overexpression of DEC1 may promote the invasiveness of breast cancer through downregulation of claudin-1. IntroductionDifferentiated embryo-chondrocyte expressed gene 1 (DEC1, also known as BHLHE40/Stra13/Sharp2) is a basic helix-loophelix (bHLH) transcription factor ubiquitously expressed in both embryonic and adult tissues (1,2). DEC1 exerts multiple biological functions, such as neurogenesis, apoptosis, cell proliferation, cell differentiation and circadian rhythms (3-8). Recent studies have revealed that the expression of DEC1 is correlated with the malignancy of a number of cancer types (9). The expression patterns of DEC1 and their impact on tumor development are largely tumor-type specific (1,9). Low DEC1 expression was found to be associated with poor histological differentiation and malignancy progression in hepatocellular carcinoma (10), whereas, overexpression of DEC1 was significantly correlated with poor survival of patients with esophageal squamous cell carcinoma following surgery (11). In breast cancer, the expression of DEC1 was found to be increased upon progression from normal tissues to invasive carcinomas (12). However, the mechanisms by which DEC1 modulates cancer progression are largely unclear.Claudin-1 is a key component of the tight junction complex and is thereby important for maintaining tight junction barrier integrity. Downregulation of claudin-1 is intimately associated with tumorigenesis in breast (13,14), prostate (15) and melanocytic neoplasia (16). It is postulated that the impact of claudin-1 on cancer invasion and metastasis is through its regulation of certain invasion/metastasis suppressors or enhancers (17,18). As significant loss of claudin-1 expression and overexpression of DEC1 are commonly observed in the progression of various types of cancers including breast cancer, we aimed to ascertain whether DEC1 modulates br...

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Claudin 1 in Breast Tumorigenesis: Revelation of a Possible Novel “Claudin High” Subset of Breast Cancers

Cited by 71 publications

References 74 publications

In utero and lactational exposure to vinclozolin and genistein induces genomic changes in the rat mammary gland

In utero and lactational exposure to vinclozolin and genistein induces genomic changes in the rat mammary gland

The expression of Claudin 1 correlates with β-catenin and is a prognostic factor of poor outcome in gastric cancer

DEC1 is positively associated with the malignant phenotype of invasive breast cancers and negatively correlated with the expression of claudin-1

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