• Title, Summary, Keyword: Dickkopf-1

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Preventable effect of L-threonate, an ascorbate metabolite, on androgen-driven balding via repression of dihydrotestosteroneinduced dickkopf-1 expression in human hair dermal papilla cells

  • Kwack, Mi-Hee;Ahn, Ji-Sup;Kim, Moon-Kyu;Kim, Jung-Chul;Sung, Young-Kwan
    • BMB Reports
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    • v.43 no.10
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    • pp.688-692
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    • 2010
  • In a previous study, we recently claimed that dihydrotestosterone (DHT)-inducible dickkopf-1 (DKK-1) expression is one of the key factors involved in androgen-potentiated balding. We also demonstrated that L-ascorbic acid 2-phosphate (Asc 2-P) represses DHT-induced DKK-1 expression in cultured dermal papilla cells (DPCs). Here, we investigated whether or not L-threonate could attenuate DHT-induced DKK-1 expression. We observed via RT-PCR analysis and enzyme-linked immunosorbent assay that DHT-induced DKK-1 expression was attenuated in the presence of L-threonate. We also found that DHT-induced activation of DKK-1 promoter activity was significantly repressed by L-threonate. Moreover, a co-culture system featuring outer root sheath (ORS) keratinocytes and DPCs showed that DHT inhibited the growth of ORS cells, which was then significantly reversed by L-threonate. Collectively, these results indicate that L-threonate inhibited DKK-1 expression in DPCs and therefore is a good treatment for the prevention of androgen-driven balding.

Dickkopf-1 is involved in BMP9-induced osteoblast differentiation of C3H10T1/2 mesenchymal stem cells

  • Lin, Liangbo;Qiu, Quanhe;Zhou, Nian;Dong, Wen;Shen, Jieliang;Jiang, Wei;Fang, Ji;Hao, Jie;Hu, Zhenming
    • BMB Reports
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    • v.49 no.3
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    • pp.179-184
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    • 2016
  • Bone morphogenetic protein 9 (BMP9) is a potent inducer of osteogenic differentiation of mesenchymal stem cells. The Wnt antagonist Dickkopf-1 (Dkk1) is involved in skeletal development and bone remodeling. Here, we investigated the role of Dkk1 in BMP9-induced osteogenic differentiation of MSCs. We found that overexpression of BMP9 induced Dkk1 expression in a dose-dependent manner, which was reduced by the P38 inhibitor SB203580 but not the ERK inhibitor PD98059. Moreover, Dkk1 dramatically decreased not only BMP9-induced alkaline phosphatase (ALP) activity but also the expression of osteocalcin (OCN) and osteopontin (OPN) and matrix mineralization of C3H10T1/2 cells. Furthermore, exogenous Dkk1 expression inhibited Wnt/β-catenin signaling induced by BMP9. Our findings indicate that Dkk1 negatively regulates BMP9-induced osteogenic differentiation through inhibition of the Wnt/β-catenin pathway and it could be used to optimize the therapeutic use of BMP9 and for bone tissue engineering.

Dickkopf-1 Levels in Turkish Patients with Bladder Cancer and its Association with Clinicopathological Features

  • Kaba, Mehmet;Pirincci, Necip;Benli, Erdal;Gecit, Ilhan;Gunes, Mustafa;Yuksel, Mehmet Bilgehan;Tok, Adem;Kemik, Ahu Sarbay
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.1
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    • pp.381-384
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    • 2014
  • Background: Evidence indicates that Dickkopf-1 (DKK-1) levels may be a biomarker for cancer risk. The aim of this study was to assess DKK-1 and its correlation with clinic-pathological features in patients with bladder cancer. Materials and Methods: DKK-1 levels were determined in serum samples from 90 patients with bladder cancer before transurethral tumor resection. The concentrations of DKK-1 were determined by using enzyme linked immune-sorbent assay (ELISA). Results: Elevated preoperative DKK-1 levels were associated with tumor stage (p<0.001), grade (p<0.001) and histological grade (p<0.001). Conclusions: The results of our study demonstrated that the level of serum DKK-1 is correlated with both disease progression and increase in the tumor grade. Preoperative serum DKK-1 elevation may thus represent a novel marker for the determination of bladder cancer and the detection of patients with a likely poor clinical outcome.

Gene Expression Altered in Endometrium of Korean Cattle with Endometritis (한우 자궁내막염에서 발현 변화를 보이는 유전자)

  • Kang, Da-Won
    • Reproductive and Developmental Biology
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    • v.31 no.3
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    • pp.207-213
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    • 2007
  • This study was carried out to examine gene expression altered in endometrium of Korean cattle (Hanwoo) with endometritis using microarray. In this study, 4,560 diferentially expressed genes (DEGs) were identified in the endometrium of Hanwoo. Of 4,560 DEGs, 2,026 genes were up-regulated, while 2,536 genes were down-regulated in endometritis. Of them, top 10 regulated genes were listed. Filamin A, pancreatic anionic trypsinogen, Rho GDP dissociation inhibitor alpha, collagen type VI alpha 1, butyrate response factor 2, aggrecanses-2, annexin 14, aminopeptidease A, orphan transporter v7-3, and epithelial stromal interaction 1 were up-regulated, while MHC class II antigen, integrin-binding sialoprotein, uterine milk protein precursor, down-regulated in colon cancer 1, glycoprotein 330, dickkopf-1, cfh protein, $Ca^{2+}-dependent$ secretion activator, UL16 binding protein 3, and proenkephalin were down-regulated in the endometritis. Our results suggest that these genes could be useful biomarkers for diagnosis Hanwoo's endometritis.

Cyclized Oligopeptide Targeting LRP5/6-DKK1 Interaction Reduces the Growth of Tumor Burden in a Multiple Myeloma Mouse Model

  • Park, Bo Mi;Kim, Eun Jin;Nam, Hee Jin;Zhang, Dongdong;Bae, Chu Hyun;Kang, Myeongmo;Kim, Heeyoun;Lee, Weontae;Bogen, Bjarne;Lim, Sung-Kil
    • Yonsei Medical Journal
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    • v.58 no.3
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    • pp.505-513
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    • 2017
  • Purpose: Dickkopf 1 (DKK1) has been extensively investigated in mouse models of multiple myeloma, which results in osteolytic bone lesions. Elevated DKK1 levels in bone marrow plasma and serum inhibit the differentiation of osteoblast precursors. Present pharmaceutical approaches to target bone lesions are limited to antiresorptive agents. In this study, we developed a cyclized oligopeptide against DKK1-low density lipoprotein receptor-related protein (LRP) 5/6 interaction and tested the effects of the oligopeptide on tumor burden. Materials and Methods: A cyclized oligopeptide based on DKK1-LRP5/6 interactions was synthesized chemically, and its nuclear magnetic resonance structure was assessed. Luciferase reporter assay and mRNA expressions of osteoblast markers were evaluated after oligopeptide treatment. MOPC315.BM.Luc cells were injected into the tail vein of mice, after which cyclized oligopeptide was delivered subcutaneously 6 days a week for 4 weeks. Results: The cyclized oligopeptide containing NXI motif bound to the E1 domain of LRP5/6 effectively on surface plasmon resonance analysis. It abrogated the $Wnt-{\beta}$-catenin signaling inhibited by DKK1, but not by sclerostin, dose dependently. RT-PCR and alkaline phosphatase staining showed increased expressions of osteoblast markers according to the treatment concentrations. Bioluminescence images showed that the treatment of cyclized oligopeptide reduced tumor burden more in oligopeptide treated group than in the vehicle group. Conclusion: The cyclized oligopeptide reported here may be another option for the treatment of tumor burden in multiple myeloma.

Assessing the Diagnostic Value of Serum Dickkopf-related Protein 1 Levels in Cancer Detection: a Case-control Study and Meta-analysis

  • Jiang, Xiao-Ting;Ma, Ying-Yu;Guo, Kun;Xia, Ying-Jie;Wang, Hui-Ju;Li, Li;He, Xu-Jun;Huang, Dong-Sheng;Tao, Hou-Quan
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.21
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    • pp.9077-9083
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    • 2014
  • Background: This study aimed to summarize the potential diagnostic value of serum DKK1 levels in cancer detection. Materials and Methods: Serum DKK1 was measured using enzyme-linked immunosorbent assay in a case-control study. Then we performed a meta-analysis and the pooled sensitivity, specificity, diagnostic odds ratio, and summary receiver operating characteristic (sROC) curves were used to evaluate the overall test performance. Results: Serum DKK1 levels were found to be significantly upregulated in gastric cancer as compared to controls. ROC curve analysis revealed an AUC of 0.636, indicating the test has the potential to diagnose cancer with poor accuracy. The summary estimates of the pooled sensitivity, specificity and diagnostic odds ratio in meta-analysis were 0.55 with a 95% confidence interval (CI) (0.53-0.57), 0.86 (95%CI, 0.84-0.88) and 12.25 (95%CI, 5.31-28.28), respectively. The area under the sROC was 0.85. Subgroup analysis revealed that the diagnostic accuracy of serum DKK1 in lung cancer (sensitivity: 0.69 with 95%CI, 0.66-0.74; specificity: 0.95 with 95%CI, 0.92-0.97; diagnostic odds ratio: 44.93 with 95%CI, 26.19-77.08) was significantly higher than for any other cancer. Conclusions: Serum DKK1 might be useful as a noninvasive method for confirmation of cancer diagnosis, particularly in the case of lung cancer.

Luciferase Assay to Screen Tumour-specific Promoters in Lung Cancer

  • Xu, Rong;Guo, Long-Jiang;Xin, Jun;Li, Wen-Mao;Gao, Yan;Zheng, You-Xian;Guo, You-Hong;Lin, Yang-Jun;Xie, Yong-Hua;Wu, Ya-Qing;Xu, Rui-An
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.11
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    • pp.6557-6562
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    • 2013
  • Objective: Specific promoters could improve efficiency and ensure the safety of gene therapy. The aim of our study was to screen examples for lung cancer. Methods: The firefly luciferase gene was used as a reporter, and promoters based on serum markers of lung cancer were cloned. The activity and specificity of seven promoters, comprising CEACAM5 (carcinoembryonic antigen, CEA), GRP (Gastrin-Releasing Peptide), KRT19 (cytokeratin 19, KRT), SFTPB (surfactant protein B, SP-B), SERPINB3 (Squamous Cell Carcinoma Antigen, SCCA), SELP (Selectin P, Granule Membrane Protein 140kDa, Antigen CD62, GMP) and DKK1 (Dickkopf-1) promoters were compared in lung cancer cells to obtain cancer-specific examples with strong activity. Results: The CEACAM5, DKK1, GRP, SELP, KRT19, SERPINB3 and SFTPB promoters were cloned. Furthermore, we successfully constructed recombinant vector pGL-CEACAM5 (DKK1, GRP, SELP, KRT19, SERPINB3 and SFTPB) contained the target gene. After cells were transfectedwith recombinant plasmids, we found that the order of promoter activity from high to low was SERPINB3, DKK1, SFTPB, KRT19, CEACAM5, SELP and GRP and the order for promoters regarding specificity and high potential were SERPINB3, DKK1, SELP, SFTPB, CEACAM5, KRT19 and GRP. Conclusion: The approach adopted is feasible to screen for new tumour specific promoters with biomarkers. In addition, the screened lung-specific promoters might have potential for use in lung cancer targeted gene therapy research.