| dickkopf WNT signaling pathway inhibitor 3 | OKDB#: 4324 |
| Symbols: | DKK3 | Species: | human | ||
| Synonyms: | RIG, REIC | Locus: | 11p15.3 in Homo sapiens |
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| General Comment | NCBI Summary: This gene encodes a protein that is a member of the dickkopf family. The secreted protein contains two cysteine rich regions and is involved in embryonic development through its interactions with the Wnt signaling pathway. The expression of this gene is decreased in a variety of cancer cell lines and it may function as a tumor suppressor gene. Alternative splicing results in multiple transcript variants encoding the same protein. [provided by RefSeq, Jul 2008] | ||||
| General function | Ligand, Extracellular binding protein | ||||
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| Cellular localization | Secreted | ||||
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| Ovarian function | Follicle atresia | ||||
| Comment | Differentially expressed genes and gene networks involved in pig ovarian follicular atresia. Terenina E et al. (2016) Ovarian folliculogenesis corresponds to the development of follicles leading to either ovulation or degeneration, this latter process being called atresia. Even if atresia involves apoptosis, its mechanism is not well-understood. The objective of this project was to analyse global gene expression in pig granulosa cells of ovarian follicles during atresia. The transcriptome analysis was performed using 9216 cDNAs microarray to identify gene networks and candidate genes involved in pig ovarian follicular atresia. One thousand six hundred and eighty four significantly regulated genes were differentially regulated between small healthy follicles and small atretic follicles. Among them, two hundred and eighty seven genes had a fold-change higher than 2 between the two follicle groups. Eleven genes (DKK3, GADD45A, CAMTA2, CCDC80, DAPK2, ECSIT, MSMB, NUPR1, RUNX2, SAMD4A, and ZNF628) having a fold-change higher than 5 between groups could likely serve as markers of follicular atresia. Moreover, automatic confrontation of deregulated genes with literature data enlightened 93 genes as regulatory candidates of pig granulosa cell atresia. Among these genes known to be inhibitors of apoptosis, stimulators of apoptosis or tumor suppressors INHBB, HNF4, CLU, different interleukins (IL5, IL24), TNF-associated receptor (TNFR1), and cytochrome-c oxidase (COX) were suggested as playing an important role in porcine atresia. Present study also enlists key upstream regulators in follicle atresia based on our results and on a literature review. The novel gene candidates and gene networks identified in the current study lead to a better understanding of the molecular regulation of ovarian follicular atresia.////////////////// | ||||
| Expression regulated by | |||||
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| Ovarian localization | Ovarian tumor | ||||
| Comment | Expression of the Wnt antagonist DKK3 is frequently suppressed in sporadic epithelial ovarian cancer. You A et al. PURPOSE: The Wnt pathway plays an important role in embryonic development, and defects in this pathway have been implicated in the tumorigenesis. The Dickkopf 3 (DKK3) is a putative Wnt signaling inhibitor that is frequently inactivated in human cancers. However, the expression of DKK3 in ovarian cancer remains unknown. METHODS: We investigated the expression of DKK3 in silico using the Digital Differential Display. DKK3 mRNA expression was also analyzed by real-time RT-PCR in ovarian carcinomas and normal ovarian tissues. DKK3 protein expression was determined by immunohistochemistry in the same ovarian carcinomas and normal ovarian tissues. RESULTS: A significantly reduced expression of DKK3 (P < 0.05) was found after comparison of normal ovary- and tumor-derived libraries in the Cancer Genome Anatomy Project (CGAP). DKK3 mRNA expression was reduced in 63% (35 of 56) of tumors compared with normal ovarian samples (P < 0.02). Analysis of 13 matched pairs of ovarian carcinomas and adjacent normal tissues showed significant transcriptional downregulation of DKK3 (>twofold) in 9 paired carcinomas (69%). Loss or weak membranous expression of DKK3 protein was observed in 66% of ovarian cancers (37 of 56) including all tumors with low transcriptional level of DKK3 gene analyzed by real-time PCR. CONCLUSIONS: To our best knowledge, this is the first time to demonstrate altered expression of DKK3 in ovarian cancer. The latter could be a relevant mechanism for the activation of the Wnt pathway in the carcinogenesis of ovarian cancer but additional studies are required to elucidate the function of DKK3 silencing in ovarian carcinogenesis. | ||||
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| Phenotypes | |||||
| Mutations | 0 mutations | ||||
| Genomic Region | show genomic region | ||||
| Phenotypes and GWAS | show phenotypes and GWAS | ||||
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| created: | June 15, 2010, 8:28 p.m. | by: |
hsueh email:
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| last update: | Dec. 14, 2016, 10 a.m. | by: | hsueh email: |
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