• Reproductive and Developmental Biology
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• v.38 no.1
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• pp.35-40
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• 2014

Beta-catenin (CTNNB1, catenin (cadherin-associated protein), beta 1) is involved in various biological processes, including embryogenesis, tumorigenesis, angiogenesis and progression of metastasis. CTNNB1, as a multifunctional and oncogenic protein, has important roles in adhesion between Sertoli cells through an N-cadherin-dependent manner and in various cancer types through its over-activation. In addition, CTNNB1 can interact with estrogen/estrogen receptor alpha complex, which regulates the transcription of WNT (wingless-type MMTV integration site family)/CTNNB1 target genes. Recently, we investigated the functional roles and expression pattern of CTNNB1 during the morphological changes of embryonic gonads of chickens and the estrogen-dependent regulation of CTNNB1 in oviduct development and potential functions as a biomarker of CTNNB1 in human epithelial ovarian cancer using the chicken as a biological research model. Therefore, in this review, we provide a new insight of potential role of CTNNB1 in the development of the female reproductive tract during early embryogenesis and ovarian carcinogenesis of laying hen models.

• Molecules and Cells
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• v.46 no.7
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• pp.441-450
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• 2023

β-Catenin (Ctnnb1) has been shown to play critical roles in the development and maintenance of epithelial cells, including the retinal pigment epithelium (RPE). Ctnnb1 is not only a component of intercellular junctions in the epithelium, it also functions as a transcriptional regulator in the Wnt signaling pathway. To identify which of its functional modalities is critically involved in mouse RPE development and maintenance, we varied Ctnnb1 gene content and activity in mouse RPE lineage cells and tested their impacts on mouse eye development. We found that a Ctnnb1 double mutant (Ctnnb1^dm), which exhibits impaired transcriptional activity, could not replace Ctnnb1 in the RPE, whereas Ctnnb1^Y654E, which has reduced affinity for the junctions, could do so. Expression of the constitutively active Ctnnb1^∆ex3 mutant also suppressed the development of RPE, instead facilitating a ciliary cell fate. However, the post-mitotic or mature RPE was insensitive to the loss, inactivation, or constitutive activation of Ctnnb1. Collectively, our results suggest that Ctnnb1 should be maintained within an optimal range to specify RPE through transcriptional regulation of Wnt target genes in the optic neuroepithelium.

• Molecules and Cells
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• v.42 no.1
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• pp.8-16
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• 2019

Mutations in the ${\beta}-catenin$ gene (CTNNB1) have been implicated in the pathogenesis of some cancers. The recent development of cancer genome databases has facilitated comprehensive and focused analyses on the mutation status of cancer-related genes. We have used these databases to analyze the CTNNB1 mutations assembled from different tumor types. High incidences of CTNNB1 mutations were detected in endometrial, liver, and colorectal cancers. This finding agrees with the oncogenic role of aberrantly activated ${\beta}-catenin$ in epithelial cells. Elevated frequencies of missense mutations were found in the exon 3 of CTNNB1, which is responsible for encoding the regulatory amino acids at the N-terminal region of the protein. In the case of metastatic colorectal cancers, in-frame deletions were revealed in the region spanning exon 3. Thus, exon 3 of CTNNB1 can be considered to be a mutation hotspot in these cancers. Since the N-terminal region of the ${\beta}-catenin$ protein forms a flexible structure, many questions arise regarding the structural and functional impacts of hotspot mutations. Clinical identification of hotspot mutations could provide the mechanistic basis for an oncogenic role of mutant ${\beta}-catenin$ proteins in cancer cells. Furthermore, a systematic understanding of tumor-driving hotspot mutations could open new avenues for precision oncology.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.29 no.4
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• pp.206-211
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• 2003

The pleomorphic adenoma is the most common neoplasm involving both the major and minor salivary glands. It is a benign, slowgrowing tumor, but local recurrences can occur. The pleomorphic adenoma gene 1 (PLAG1), which is a novel zinc finger gene, is frequently activated by reciprocal chromosomal translocations involving 8q12 in a subset of salivary gland pleomorphic adenomas. This experimental study was preformed to observe the translocation patterns between PLAG1 gene and the three translocation partner genes. We also have analyzed the presence of PLAG1 transcripts by RT-PCR. CTNNB1/PLAG1 gene fusion was observed in three of nine pleomorphic adnomas. However, LIFR/PLAG1 and SII/PLAG1 gene fusions were not detectable. All of three gene fusions was not detectable in one Warthin's tumor and three inflammatory salivary gland tissues. PLAG1 transcripts were expressed in all inflammatory salivary gland tissues and tumors except for three pleomorphic adenomas. Of particular one pleomorphic adenoma showing CTNNB1/PLAG1 gene fusion did not express PLAG1 transcipt. Our data indicate that gene fusion involving PLAG1 is a frequent event in pleomorphic adenoma, but correlation between gene fusion involving PLAG1 and PLAG1 transcription is not definite.

• Animal Bioscience
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• v.34 no.6
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• pp.957-966
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• 2021

Objective: Ovarian follicular development, which dependent on the proliferation and differentiation of granulosa cells (GCs), is a complex biological process in which miRNA plays an important role. Our previous study showed that miR-458b-5p is associated with ovarian follicular development in chicken. The detailed function and molecular mechanism of miR-458b-5p in GCs is unclear. Methods: The luciferase reporter assay was used to verify the targeting relationship between miR-458b-5p and catenin beta-1 (CTNNB1), which is an important transcriptional regulatory factor of the Wnt/β-catenin pathway. The cell counting kit-8 (CCK-8) assay, flow cytometry with propidium iodide (PI) and annexin V-fluorescein isothiocyanate (FITC) labeling were applied to explore the effect of miR-458b-5p on proliferation, cell cycle and apoptosis of chicken GCs. Quantitative real-time polymerase chain reaction and Western blot were used to detect the mRNA and protein expression levels. Results: We demonstrated that the expression of miR-458b-5p and CTNNB1 showed the opposite relationship in GCs and theca cells of hierarchical follicles. The luciferase reporter assay confirmed that CTNNB1 is the direct target of miR-458b-5p. Using CCK-8 assay and flow cytometry with PI and Annexin V-FITC labeling, we observed that transfection with the miR-458b-5p mimics significantly reduced proliferation and has no effects on apoptosis of chicken GCs. In addition, miR-458b-5p decreased the mRNA and protein expression of CD44 molecule and matrix metallopeptidase 7, which are the downstream effectors of CTNNB1 in Wnt/β-Catenin pathway and play functional roles in cell proliferation. Conclusion: Taken together, the data indicate that miR-458b-5p regulates ovarian GCs proliferation through Wnt/β-catenin signaling pathway by targeting CTNNB1, suggesting that miR-458b-5p and its target gene CTNNB1 may potentially play a role in chicken ovarian follicular development.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2527-2532
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• 2012

Objectives: The aim of the present study was to explore mechanisms underlying the effects of down-regulating ${\beta}$-catenin expression on esophageal carcinoma (EC) cells. Methods: Cell cycle distribution and apoptosis were determined using flow cytometry and annexin V apoptosis assay, respectively. Transmission electron microscopy (TEM) was used to examine changes in ultrastructure, while expression of cyclin D1 protein and mRNA was detected by western blot and real-time PCR. Proliferating cell nuclear antigen (PCNA) and extracellular signal-regulated kinase (ERK) 1-2 were evaluated by Western blot analysis. PCNA labeling index (LI) was determined by immunocytochemistry. Results: Compared with pGen-3-con transfected and Eca-109 cells, the percentage of G0/G1-phase pGen-3-CTNNB1 transfected cells was obviously increased (P<0.05), with no significant difference among the three groups with regard to apoptosis (P>0.05). pGen-3-CTNNB1 transfected cells exhibited obvious decrease in cyclin D1 mRNA and protein expression (P<0.05) and the ultrastructure of Eca-109 cells underwent a significant change after being transfected with pGen-3-CTNNB1, suggesting that down-regulating ${\beta}$-catenin expression can promote the differentiation and maturation. The expression of PCNA and the ERKI/2 phosphorylation state were also down-regulated in pGen-3-CTNNB1 transfected cells (P<0.05). At the same time, the PCNA labeling index was decreased accordingly (P<0.05). Conclusion: Inhibition of EC Eca-109 cellproliferation by down-regulating ${\beta}$-catenin expression could improve cell ultrastructure by mediating blockade in G0/G1 through inhibiting cyclin D1, PCNA and the MAPK pathway (p-ERK1/2).

• Genomics & Informatics
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• v.19 no.2
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• pp.14.1-14.6
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• 2021

Coronavirus disease 2019 (COVID-19) is an on-going pandemic disease infecting millions of people across the globe. Recent reports of reduction in antibody levels and the re-emergence of the disease in recovered patients necessitated the understanding of the pandemic at the core level. The cases of multiple organ failures emphasized the consideration of different organ systems while managing the disease. The present study employed RNA sequencing data to determine the disease associated differentially regulated genes and their related protein interactions in several organ systems. It signified the importance of early diagnosis and treatment of the disease. A map of protein interactions of multiple organ systems was built and uncovered CAV1 and CTNNB1 as the top degree nodes. A core interactions sub-network was analyzed to identify different modules of functional significance. AR, CTNNB1, CAV1, and PIK3R1 proteins were unfolded as bridging nodes interconnecting different modules for the information flow across several pathways. The present study also highlighted some of the druggable targets to analyze in drug re-purposing strategies against the COVID-19 pandemic. Therefore, the protein interactions map and the modular interactions of the differentially regulated genes in the multiple organ systems would incline the scientists and researchers to investigate in novel therapeutics for the COVID-19 pandemic expeditiously.

• Biomolecules & Therapeutics
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• v.28 no.6
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• pp.491-502
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• 2020

Sex/gender disparity has been shown in the incidence and prognosis of many types of diseases, probably due to differences in genes, physiological conditions such as hormones, and lifestyle between the sexes. The mortality and survival rates of many cancers, especially liver cancer, differ between men and women. Due to the pronounced sex/gender disparity, considering sex/gender may be necessary for the diagnosis and treatment of liver cancer. By analyzing research articles through a PubMed literature search, the present review identified 12 genes which showed practical relevance to cancer and sex disparities. Among the 12 sex-specific genes, 7 genes (BAP1, CTNNB1, FOXA1, GSTO1, GSTP1, IL6, and SRPK1) showed sex-biased function in liver cancer. Here we summarized previous findings of cancer molecular signature including our own analysis, and showed that sex-biased molecular signature CTNNB1^High, IL6^High, RHOA^High and GLIPR1^Low may serve as a female-specific index for prediction and evaluation of OS in liver cancer patients. This review suggests a potential implication of sex-biased molecular signature in liver cancer, providing a useful information on diagnosis and prediction of disease progression based on gender.

• Proceedings of the Korean Society of Toxicology Conference
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• 2001.10b
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• pp.5-6
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• 2001

The carcinogens 2-arnioo-3-methylimidazo［4,5-f］quinoline (IQ) and 1,2-dimethylhydrazine (DMH) induce colon tumors in the Fisher 344 rat that contain mutations in Ctnnb1, the gene for b-catenin, but the pattern of mutation differs from that found in human colon cancers. in both species, mutations affect the glycogen synthase kinase 3$\beta$ (GSK-3$\beta$) consensus region of $\beta$-catenin, but whereas they directly substitute critical Ser/Thr phosphorylation sites in human colon cancers, the majority of mutations cluster around Ser$^{33}$ in the rat tumors.(omitted)

• Archives of Craniofacial Surgery
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• v.21 no.3
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• pp.176-179
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• 2020

Pilomatricoma is a benign tumor arising from the primitive basal cells of the epidermis that differentiate into hair matrix cells. Mutations in the CTNNB1 gene, which encodes β-catenin (a protein involved in hair growth), play an etiological role in the development of pilomatricoma. A 34-year-old woman presenting with a mass in the right parotid region underwent an excisional biopsy. The mass was conclusively diagnosed as pilomatricoma. During pregnancy, the mass grew from 1 cm to 5 cm in diameter and was accompanied by pain and tenderness. The growth may have been facilitated by the increased production of estrogen and progesterone, which bind to receptors located in the outer root sheath cells of the hair follicles. No recurrence was observed during 6 months of follow-up.