• Asian Pacific Journal of Cancer Prevention
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• v.13 no.1
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• pp.371-376
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• 2012

Background: Caveolin-1 (CAV-1), encoding the structural component of cellular caveolae, is a suggested tumor suppressor gene involved in cell signalling. Aberrant promoter methylation of CAV-1 is associated with inactivation of expression. We previously observed CAV-1 mutations in breast cancers and therefore devised this study to examine the hypermethylation status of the promoter region of CAV-1 with reference to breast cancer progression and development. Methods: Hypermethylation status of CAV-1 was analyzed by methylation specific PCR. Loss of expression of the CAV-1 gene was further evaluated by semi-quantitative rt-PCR. Results: 28/130 (21.5%) breast cancer cases showed promoter hypermethylation with reduced CAV-1 expression levels when compared with adjacent normal breast tissue. CAV-1 gene hypermethylation was significantly related to menopausal status, histopathological grade and age. Conclusion: The rationale of our study is that CAV-1 gene is transcriptionally repressed in breast cancer cells due to hypermethylation. Our results reveal that promoter hypermethylation and loss of expression of the CAV-1 gene is an important alternative mechanism for inactivation of CAV-1 leading to complete gene silencing.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.19
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• pp.8367-8370
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• 2014

The relationship between caveolin-1 (Cav-1) and clinicopathological characteristics of gastric cancer is controversial, although Cav-1 plays an important role in tumor metastasis. To evaluate the clinicopathological and prognostic value of expression in patients with gastric cancer, a meta-analysis was performed to investigate the impact on clinicopathological parameters and prognosis in gastric cancer cases. Studies assessing these parameters for Cav-1 in gastric cancer were identified up to June 2014. Finally, a total of six studies met the inclusion criteria. Our combined results showed that Cav-1 expression was significantly associated with the Lauren classification (pooled OR=0.603, 95% CI: 0.381-0.953, P=0.030). Furthermore, we found that Cav-1 expression predicted a better overall survival in gastric cancer patients (pooled OR=0.590, 95% CI: 0.360-0.970, P=0.038, fixed-effect). In conclusion, the overall data of the present meta analysis showed that Cav-1 expression was not correlated with clinicopathological features except for the Lauren classification. Simultaneously, Cav-1 overexpression predicted a better overall survival in gastric cancer. Cav-1 expression in tumors is a candidate positive prognostic biomarker for gastric cancer patients.

• Journal of Applied Biological Chemistry
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• v.66
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• pp.311-319
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• 2023

Caveolin-1 (Cav-1) is the main structural component of the caveolae on the plasma membrane, which regulates various cellular processes, including cell growth, differentiation, and endocytosis. Although a recent study demonstrated that Cav-1 might be involved in diabetes-associated inflammation, its exact role in the intestine was unclear. In this study, we examined the intestinal expression of Cav-1 in diabetic conditions. We also investigated its effect on lipopolysaccharide (LPS)-induced inflammation by expressing this protein in human intestinal Caco-2 cells lacking Cav-1. We observed that increased Cav-1 levels and decreased expression of tight junction proteins affected intestinal permeability in high-fat diet-induced diabetic mice. When Caco-2 cells were treated with LPS, Cav-1 enhanced the NF-κB signaling. Moreover, LPS reduced the expression of tight junction proteins while it increased cell-cell permeability and reactive oxygen species generation in Caco-2 cells and this effect was amplified by cav-1 overexpression. LPS treatment promoted phosphorylation of tyrosine-14 (Y14) on Cav-1, and the LPS-induced NF-κB signaling was suppressed in cells expressing non-phosphorylatable Cav-1 (tyrosine-14 to phenylalanine mutant), which reduced intestinal barrier permeability. These results suggest that Cav-1 expression promotes LPS-induced inflammation in Caco-2 cells, and phosphorylation of Y14 on Cav-1 might contribute to the anti-inflammatory response in LPS-induced NF-κB signaling and cell permeability.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.16
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• pp.6803-6812
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• 2015

Caveolin-1 is a 22-kD trans-membrane protein enriched in particular plasma membrane invaginations known as caveolae. Cav-1 expression is often dysregulated in human breast cancers, being commonly upregulated in cancer cells and downregulated in stromal cells. As an intracellular scaffolding protein, Cav-1, is involved in several vital biological regulations including endocytosis, transcytosis, vesicular transport, and signaling pathways. Several pathways are modulated by Cav-1 including estrogen receptor, EGFR, Her2/neu, $TGF{\beta}$, and mTOR and represent as major drivers in mammary carcinogenesis. Expression and role of Cav-1 in breast carcinogenesis is highly variable depending on the stage of tumor development as well as context of the cell. However, recent data have shown that downregulation of Cav-1 expression in stromal breast tumors is associated with frequent relapse, resistance to therapy, and poor outcome. Modification of Cav-1 expression for translational cancer therapy is particularly challenging since numerous signaling pathways might be affected. This review focuses on present understanding of Cav-1 in breast carcinogenesis and its potential role as a new biomarker for predicting therapeutic response and prognosis as well as new target for therapeutic manipulation.

• Molecules and Cells
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• v.45 no.12
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• pp.950-962
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• 2022

Aging is a major risk factor for common neurodegenerative diseases. Although multiple molecular, cellular, structural, and functional changes occur in the brain during aging, the involvement of caveolin-2 (Cav-2) in brain ageing remains unknown. We investigated Cav-2 expression in brains of aged mice and its effects on endothelial cells. The human umbilical vein endothelial cells (HUVECs) showed decreased THP-1 adhesion and infiltration when treated with Cav-2 siRNA compared to control siRNA. In contrast, Cav-2 overexpression increased THP-1 adhesion and infiltration in HUVECs. Increased expression of Cav-2 and iba-1 was observed in brains of old mice. Moreover, there were fewer iba-1-positive cells in the brains of aged Cav-2 knockout (KO) mice than of wild-type aged mice. The levels of several chemokines were higher in brains of aged wild-type mice than in young wild-type mice; moreover, chemokine levels were significantly lower in brains of young mice as well as aged Cav-2 KO mice than in their wild-type counterparts. Expression of PECAM1 and VE-cadherin proteins increased in brains of old wild-type mice but was barely detected in brains of young wild-type and Cav-2 KO mice. Collectively, our results suggest that Cav-2 expression increases in the endothelial cells of aged brain, and promotes leukocyte infiltration and age-associated neuroinflammation.

• The Korean Journal of Physiology and Pharmacology
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• v.12 no.4
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• pp.143-148
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• 2008

Caveolin-1 (CAV1) is an integral membrane protein that may function as a scaffold for plasma membrane proteins and acts as a tumor suppressor protein. One causative factor of chemotherapy-resistant cancers is P-plycoprotein (P-gp), the product of the multidrug resistance-1 gene (MDR1), which is localized in the caveolar structure. Currently, the interactive roles of CAV1 and MDR1 expression in the death of cancer cells remain controversial. In this study, we investigated the effects of indomethacin on the cell viability and the expression levels of MDR1 mRNA and protein in a CAV1-siRNA-mediated gene knockdown hepatoma cell line (SK-Hep1). Cell viability was significantly decreased in CAV1-siRNA-transfected cells compared with that of control-siRNA-transfected cells. Furthermore, the viability of cells pretreated with CAV1 siRNA was markedly decreased by treatment with indomethacin (400${\mu}$M for 24 h). However, the protein and mRNA levels of MDR1 were unchanged in CAV1-siRNA-transfected cells. These results suggest that CAV1 plays an important role as a major survival enzyme in cancer cells, and indomethacin can sensitively induce cell death under conditions of reduced CAV1 expression, independent of MDR1 expression.

• Journal of Veterinary Science
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• v.23 no.5
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• pp.63.1-63.14
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• 2022

Background: Chicken anemia virus (CAV) causes chicken infectious anemia, which results in immunosuppression; the virus has spread widely in chicken flocks in China. Objectives: The aim of this study was to understand recent CAV genetic evolution in chicken flocks in Guangxi Province, southern China. Methods: In total, 350 liver samples were collected from eight commercial broiler chicken farms in Guangxi Province in southern China from 2018 to 2020. CAV was detected by conventional PCR, and twenty CAV complete genomes were amplified and used for the phylogenetic analysis and recombination analysis. Results: The overall CAV-positive rate was 17.1%. The genetic analysis revealed that 84 CAVs were distributed in groups A, B, C (subgroups C1-C3) and D. In total, 30 of 47 Chinese CAV sequences from 2005-2020 belong to subgroup C3, including 15 CAVs from this study. There were some specific mutation sites among the intergenotypes in the VP1 protein. The amino acids at position 394Q in the VP1 protein of 20 CAV strains were consistent with the characteristics of a highly pathogenic strain. GX1904B was a putative recombinant. Conclusions: Subgroup C3 was the dominant genotype in Guangxi Province from 2018-2020. The 20 CAV strains in this study might be virulent according to the amino acid residue analysis. These data help improve our understanding of the epidemiological trends of CAV in southern China.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.4
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• pp.2295-2299
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• 2013

Background: To explore the role of caveolin-1(CAV-1) gene silencing on MAPK activation in lipopolysaccharide (LPS)-challenged human mammary epithelial cells. Methods: We established a MCF-10ACE of CAV-1 gene silencing from human mammary epithelial cell line MCF-10A by RNAi technology. DNA Microarray were used to detect the expression of inflammation-associated genes in MCF10ACE. Western blotting was used to examine the activation of MAPK in lipopolysaccharide(LPS)-challenged MCF-10A and MCF-10ACE. Moreover, immunofluorescence and Western bloting were performed to detect the co-localization of CAV-1 and toll-like receptor 4 (TLR4) in human mammary epithelial cells. Results: MCF-10ACE exhibited significant increases in inflammation-associated gene expression, especially IL-6 (~7-fold) and IL6R (~17-fold). In addition, LPS-induced p38 MAPK and JNK MAPK activation was significantly increased in MCF-10ACE. Furthermore, CAV-1 co-localized with TLR4 and appeared a negative correlation trend. Conclusion: CAV-1 gene silencing promotes MAPK activation via TLR4 signaling in human mammary epithelial cells response to LPS.

• Journal of Animal Science and Technology
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• v.49 no.6
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• pp.719-728
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• 2007

The cysteine and glycine rich protein 3 (CSRP3), apolipoprotein B mRNA editing enzyme catalytic polypeptide‐like 2(APOBEC2) and caveolin (CAV) gene family(CAV1, CAV2, CAV3) have been reported to play important roles for carcass and meat quality traits in pig, mouse, human and cattle. As an initial step, we investigated SNPs in these 5 genes among eight different cattle breeds. Eighteen primer pairs were designed from bovine sequence data of NCBI database to amplify the partial gene fragments. Sequencing results revealed 9 SNPs in the coding regions of three caveolin genes, 1 SNP in CSRP3 and 3 SNPs in APOBEC2 gene. All the identified SNPs were confirmed by PCR-RFLP. Also, 9 more intronic SNPs were detected in these genes. However, all identified mutations in the coding region do not change amino acid sequence. Allelic distributions were significantly different for 5 SNPs in CAV2, CAV3, CSRP3 and APOBEC2 genes among the eight different breeds. These results gave some clues about the polymorphisms of these genes among the cattle breeds and will be useful for further searches for identifying association between these SNPs and meat quality traits in cattle.

• Korean Journal of Veterinary Service
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• v.41 no.1
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• pp.21-27
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• 2018

Fowl adenovirus (FAdV) and chicken anemia virus (CAV) have gained much importance as an immunosuppressive and economically important emerging pathogen of poultry. This study was carried out to investigate the prevalence of FAdV and CAV infection in chickens. The groups were divided into Korean native chickens, broiler, layer hens and broiler breeder and set up groups according to age. As results, 12.5% of the native chicken, 2.5% of broiler and 6.7% of layer chicken were positive, respectively by PCR for FAdV. Serological test showed that 84.8%, 79.0%, 97.7% and 96.1% of chickens were positive for antibody to FAdV in native chickens, broiler, layer hens and broiler breeder. The prevalence of CAV infection were 20.0%, 7.5%, 16.7% and 10.0%, based on CAV gene detection by PCR. In serological test of CAV, 40.6%, 35.9%, 84.8% and 73.9% of chickens were positive in that groups.