Analysis of Cellular Changes Resulting from Forced Expression of Dickkopf-1 in Hepatocellular Carcinoma Cells
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Recent studies have shown that Dickkopf-1 (DKK-1) is overexpressed in some tumors, including hepatocellular carcinoma. However, the role of increased DKK-1 in these tumors is not known. In this study, the DKK-1 expression in hepatocellular carcinoma (HCC) cell lines was evaluated and the effect of DKK-1 overexpression in HCC cell lines was studied. Materials and Methods: The expression of DKK-1 in hepatocellular carcinoma cell lines was evaluated by RT-PCR. Stable cell lines that overexpressed DKK-1 were established. Cell growth, adhesion, migration and invasion assays were performed. Results: RT-PCR analysis showed that 5 out of 8 HCC cell lines expressed DKK-1. The forced expression of DKK-1 suppressed the growth of cells and increased the population of cells in the sub-G1 phase. In addition, DKK- 1 reduced the cellular adhesion capacity to collagen type I and fibronectin, and it increased migratory capacity. However, overexpression of DKK-1 did not increase the invasion capacity of the HCC cell line. Conclusion: Collectively, our data suggest that overexpression of DKK-1 affects the biology of HCC cells. (Cancer Res Treat. 2007;39:30-36)
Abstract
Recent studies have shown that Dickkopf-1 (DKK-1) is overexpressed in some tumors, including hepatocellular carcinoma. However, the role of increased DKK-1 in these tumors is not known. In this study, the DKK-1 expression in hepatocellular carcinoma (HCC) cell lines was evaluated and the effect of DKK-1 overexpression in HCC cell lines was studied. Materials and Methods: The expression of DKK-1 in hepatocellular carcinoma cell lines was evaluated by RT-PCR. Stable cell lines that overexpressed DKK-1 were established. Cell growth, adhesion, migration and invasion assays were performed. Results: RT-PCR analysis showed that 5 out of 8 HCC cell lines expressed DKK-1. The forced expression of DKK-1 suppressed the growth of cells and increased the population of cells in the sub-G1 phase. In addition, DKK- 1 reduced the cellular adhesion capacity to collagen type I and fibronectin, and it increased migratory capacity. However, overexpression of DKK-1 did not increase the invasion capacity of the HCC cell line. Conclusion: Collectively, our data suggest that overexpression of DKK-1 affects the biology of HCC cells. (Cancer Res Treat. 2007;39:30-36)
참고문헌 (20)
- Miler JR, "The Wnts", 3, pp.1~15 (2003)
- Gonzalez-Sancho JM, "The Wnt antagonist DICKKOPF-1 gene is a downstream target of beta-catenin", TCF and is downregulated in human colon cancer, 2005, pp.24, 1098~1103
- Krupnik VE, "Functional and structural diversity of the human Dickkopf gene family", 238, pp.301~313 (1999)
- Niida A, "DKK1, a negative regulator of Wnt signaling, is a target of the beta-catenin", TCF pathway, 2004, pp.23, 8520~8526
- Aguilera O, "Epigenetic inactivation of the Wnt antagonist DICKKOPF-1 (DKK-1) gene in human colorectal cancer", 25, pp.4116~4121 (2006)
- Lee AY, "Dickkopf-1 antagonizes Wnt signaling independent of beta- catenin in human mesothelioma", 323, pp.1246~1250 (2004)
- Mikheev AM, "A functional genomics approach for the identification of putative tumor suppressor genes: Dickkopf-1 as suppressor of HeLa cell transformation", 25, pp.47~59 (2004)
- Wirths O, "Overexpression of human Dickkopf-1, an antagonist of wingless", WNT signaling, in human hepatoblastomas and Wilms' tumors, 2003, pp.83, 429~434
- Patil MA, "An integrated data analysis approach to characterize genes highly expressed in hepatocellular carcinoma", 24, pp.3737~3742 (2005)
- Park JG, "Characterization of cell lines established from human hepatocellular carcinoma", 62, pp.276~282 (1995)
- Farooq M, "Blocking endogenous glypican-3 expression releases Hep 3B cells from G1 arrest", 15, pp.356~360 (2003)
- Glinka A, "Dickkopf-1 is a member of a new family of secreted proteins and functions in head induction", 391, pp.357~362 (1998)
- de la Coste A, "Somatic mutations of the beta-catenin gene are frequent in mouse and human hepatocellular carcinomas", 95, pp.8847~8851 (1998)
- Boyault S, "Transcriptome classification of HCC is related to gene alterations and to new therapeutic targets", 45, pp.42~52 (2007)
- Kondo Y, "Beta-catenin accumulation and mutation of exon 3 of the beta-catenin gene in hepatocellular carcinoma", 90, pp.1301~1309 (1999)
- Taniguchi K, "Mutational spectrum of beta-catenin, AXIN1, and AXIN2 in hepatocellular carcinomas and hepatoblastomas", 21, pp.4863~4871 (2002)
- Park JY, "Mutations of beta-catenin and AXIN I genes are a late event in human hepatocellular carcinogenesis", 25, pp.70~76 (2005)
- Merle P, "Functional consequences of frizzled-7 receptor overexpression in human hepatocellular carcinoma", 127, pp.1110~1122 (2004)
- Shou J, "Human Dkk-1, a gene encoding a Wnt antagonist, responds to DNA damage and its overexpression sensitizes brain tumor cells to apoptosis following alkylation damage of DNA", 21, pp.878~889 (2002)
- Aplin AE, "Cell adhesion molecules, signal transduction and cell growth", 11, pp.737~744 (1999)