Disease relevance of CLDN3

• RESULTS: Although expressed at low levels in some normal human tissues, including the ovary, CLDN3 and CLDN4 are highly up-regulated in epithelial ovarian cancers of all subtypes [1].
• Tight junction proteins claudin-3 and claudin-4 are frequently overexpressed in ovarian cancer but not in ovarian cystadenomas [1].
• No statistical differences were detected for OCLN and CLDN-3 between the edema group and healthy controls [2].
• There was a significantly elevated expression (p<0.01) on mRNA and protein level between the leg ulcer group and healthy controls for OCLN and CLDN-3 [2].
• The persistent high level of claudin-3 expression in prostate adenocarcinoma and functional cytotoxicity of CPE in metastatic androgen-independent prostate adenocarcinoma suggests a new potential therapeutic strategy for prostate cancer [3].

High impact information on CLDN3

• Leaky epithelium in gammadelta(+) iIEL-deficient mice was associated with the absence of phosphorylation of serine residues of occludin and lack of claudin 3 and zona occludens-1 proteins in TJ complexes [4].
• Upon induction by Egr-1, Snail represses the expression of E-cadherin and claudin-3 genes [5].
• Our previous studies have revealed that claudin-3 and claudin-4 proteins are highly overexpressed in ovarian cancer [6].
• Using expression profiling, we and others have recently found claudin-3 and claudin-4 genes to be highly expressed in ovarian cancer [7].
• In particular, claudin-3 and claudin-4 are frequently overexpressed in several neoplasias, including ovarian, breast, pancreatic, and prostate cancers [8].

Chemical compound and disease context of CLDN3

• Phosphorylation of claudin-3 at threonine 192 by cAMP-dependent protein kinase regulates tight junction barrier function in ovarian cancer cells [9].

Biological context of CLDN3

• CONCLUSIONS: These results suggest that up-regulation of DDR1, CLDN3, and epithelial cell adhesion molecule are early events in the development of EOC and have potential application in the early detection of disease [10].
• In ovarian cancer cell lines, claudin-3 and claudin-4 expression was not associated with functional TJs as measured by transepithelial electrical resistance [1].
• The two genes with the highest inverse association with invasion, TACSTD1 and CLDN3, are involved with cell adhesion and cell-cell interactions, respectively [11].
• Concerning relation to Federation for International Gynaecology and Obstetrics (FIGO) grade, claudin 3, but not claudin 4, was significantly increased in moderately, poorly and undifferentiated adenocarcinomas compared to well-differentiated and borderline-type tumours [12].
• Selected serial analysis of gene expression results were further validated through immunohistochemical analysis of ApoJ, claudin-3, claudin-4, and epithelial cellular adhesion molecule in archival material [13].

Anatomical context of CLDN3

• RESULTS: We confirmed that these genes are highly overexpressed in all histological subtypes of EOC compared with normal ovarian surface epithelium, identifying DDR1 and CLDN3 as new biomarkers of EOC [10].
• CONCLUSIONS: These results show that CLDN3 and CLDN4 are frequently up-regulated in ovarian tumors and cell lines and may represent novel markers for this disease [1].
• While normal gastric mucosa lacked Claudin 3, 4, and 7 expression, intestinal metaplasia and dysplasia showed these proteins [14].
• By microarray analysis, Claudin 3 showed a marked increase in mRNA expression compared with normal esophagus (approximately 100-fold) [14].
• High levels of expression of CPE-R and/or RVP1 mRNA were also detected in other organs, including the lungs, liver, and kidneys, but only low levels were expressed in heart and skeletal muscles [15].

Associations of CLDN3 with chemical compounds

• They were classified into two groups, the Vero cell CPE receptor homologues and rat androgen withdrawal apoptosis protein (RVP1; accession no. M74067) homologues, based on the similarities of primary amino acid sequences [15].
• In vitro phosphorylation assays using glutathione S-transferase fusion constructs demonstrated that the C terminus of claudin-3 is an excellent substrate for cAMP-dependent protein kinase (PKA) [9].

Other interactions of CLDN3

• We also investigated whether high expression of claudin-3 and claudin-4 was associated with TJ function in ovarian cancer cells [1].
• METHODS: Altogether, 56 sections from 52 surgically resected breast specimens were analyzed for CLDN1, CLDN3 and CLDN4 expression by immunohistochemistry. mRNA was also analyzed using real-time PCR in 17 of the 52 cases [16].
• Membrane-bound claudin 3 and 4 expression was seen in all cases of Paget's disease, whereas claudin 5 was seen in 50% of cases and claudin 2 was seen in 32% of cases [17].
• Following induction of differentiation by pharmacological activation of PPARgamma and blockade of EGFR, there was de novo expression of claudin 3 mRNA and protein and downregulation of claudin 2 transcription [18].
• Northern blotting and semi-quantitative RT-PCR demonstrated that claudin 5 was expressed in RPE, but claudin 3 was expressed only in the choroid layer of the eye [19].

Analytical, diagnostic and therapeutic context of CLDN3

• On human multiple-tissue Northern blot analysis, mRNAs for both claudin-3 and claudin-4 were expressed at high levels in prostate tissue [3].
• Using site-directed mutagenesis, we identified a PKA phosphorylation site at amino acid 192 in the C terminus of claudin-3 [9].
• Using RT-PCR we have identified mRNA transcripts for Cldn-3 through -9 in each region of the adult rat epididymis [20].
• A parallel study of claudin tight junction proteins in endoscopy biopsy samples showed that whereas Barrett's metaplasia contains dramatically more claudin-2 and claudin-3 than is found in normal esophageal mucosa, it is markedly lower in claudins 1 and 5, indicating very different tight junction barriers [21].

References