AIM: To investigate the mechanisms of the biological roles of Dickkopf-3 (Dkk-3) in cell invasion, survival and apoptosis in colon cancer cells. METHODS: Three human colon cancer cell lines, i.e., HT-29, LoVo and SW480, were used. Overexpression of Dkk-3 induced by pEGFP-N1-Dkk-3-GFP plasmid in LoVo cells was performed using Lipofectamine 2000 reagent. Reverse transcription polymerase chain reaction and Western blotting were performed to determine the mRNA and protein expression levels of Dkk-3, respectively. Cell proliferation assay, cell cycle analysis, hoechst 33258 assay and Matrigel invasion assay were performed on Dkk-3 overexpressing transfectants. RESULTS: The mRNA and protein expressions of Dkk-3 in HT-29 (mRNA: 0.06 ± 0.02, protein: 0.06 ± 0.01) and LoVo (mRNA: 0.07 ± 0.02, protein: 0.07 ± 0.02) cells were significantly lower than that in SW480 cells (mRNA: 0.92 ± 0.04, protein: 0.69 ± 0.13; all P < 0.05), and the greatest levels of invasiveness was in LoVo cells. Dkk-3 overexpression inhibited the proliferation and invasion of LoVo cells and induced cell cycle arrest at G(0)/G(1) phase and subsequent apoptosis, as indicated by increased chromatin condensation and fragments, upregulated Bax and cytochrome c protein, downregulated survivin and Bcl-2 protein, and the activation of caspase-3 and caspase-9. Furthermore, Dkk-3 overexpression reduced the accumulation of cytosolic fraction of β-catenin. CONCLUSION: Dkk-3 overexpression induced apoptosis in human colon cancer possibly through the mitochondrial pathway. Dkk-3 may be involved in the Wnt/β-catenin signaling pathways in colon cancer.
AIM: To investigate the mechanisms of the biological roles of Dickkopf-3 (Dkk-3) in cell invasion, survival and apoptosis in colon cancer cells. METHODS: Three humancolon cancer cell lines, i.e., HT-29, LoVo and SW480, were used. Overexpression of Dkk-3 induced by pEGFP-N1-Dkk-3-GFP plasmid in LoVo cells was performed using Lipofectamine 2000 reagent. Reverse transcription polymerase chain reaction and Western blotting were performed to determine the mRNA and protein expression levels of Dkk-3, respectively. Cell proliferation assay, cell cycle analysis, hoechst 33258 assay and Matrigel invasion assay were performed on Dkk-3 overexpressing transfectants. RESULTS: The mRNA and protein expressions of Dkk-3 in HT-29 (mRNA: 0.06 ± 0.02, protein: 0.06 ± 0.01) and LoVo (mRNA: 0.07 ± 0.02, protein: 0.07 ± 0.02) cells were significantly lower than that in SW480 cells (mRNA: 0.92 ± 0.04, protein: 0.69 ± 0.13; all P < 0.05), and the greatest levels of invasiveness was in LoVo cells. Dkk-3 overexpression inhibited the proliferation and invasion of LoVo cells and induced cell cycle arrest at G(0)/G(1) phase and subsequent apoptosis, as indicated by increased chromatin condensation and fragments, upregulated Bax and cytochrome c protein, downregulated survivin and Bcl-2 protein, and the activation of caspase-3 and caspase-9. Furthermore, Dkk-3 overexpression reduced the accumulation of cytosolic fraction of β-catenin. CONCLUSION:Dkk-3 overexpression induced apoptosis in humancolon cancer possibly through the mitochondrial pathway. Dkk-3 may be involved in the Wnt/β-catenin signaling pathways in colon cancer.
Authors: Silke Radetzki; Claus-Henning Köhne; Clarissa von Haefen; Bernhard Gillissen; Isrid Sturm; Bernd Dörken; Peter T Daniel Journal: Oncogene Date: 2002-01-10 Impact factor: 9.867
Authors: V E Krupnik; J D Sharp; C Jiang; K Robison; T W Chickering; L Amaravadi; D E Brown; D Guyot; G Mays; K Leiby; B Chang; T Duong; A D Goodearl; D P Gearing; S Y Sokol; S A McCarthy Journal: Gene Date: 1999-10-01 Impact factor: 3.688
Authors: Koji Ueno; Hiroshi Hirata; Shahana Majid; Yi Chen; Mohd S Zaman; Z Laura Tabatabai; Yuji Hinoda; Rajvir Dahiya Journal: Mol Carcinog Date: 2011-01-25 Impact factor: 4.784
Authors: Bang H Hoang; Tadahiko Kubo; John H Healey; Rui Yang; Saminathan S Nathan; E Anders Kolb; BethAnne Mazza; Paul A Meyers; Richard Gorlick Journal: Cancer Res Date: 2004-04-15 Impact factor: 12.701
Authors: J Roman-Gomez; A Jimenez-Velasco; X Agirre; J A Castillejo; G Navarro; M Barrios; E J Andreu; F Prosper; A Heiniger; A Torres Journal: Br J Cancer Date: 2004-08-16 Impact factor: 7.640
Authors: Pan Pan; Kiyoko Oshima; Yi-Wen Huang; Kimberle A Agle; William R Drobyski; Xiao Chen; Jianying Zhang; Martha M Yearsley; Jianhua Yu; Li-Shu Wang Journal: Int J Cancer Date: 2018-03-30 Impact factor: 7.396
Authors: Adam A Kraya; Shengfu Piao; Xiaowei Xu; Gao Zhang; Meenhard Herlyn; Phyllis Gimotty; Beth Levine; Ravi K Amaravadi; David W Speicher Journal: Autophagy Date: 2015 Impact factor: 16.016
Authors: Carol H Lin; Yi Guo; Samia Ghaffar; Peter McQueen; Jonathan Pourmorady; Alexander Christ; Kevin Rooney; Tao Ji; Ramez Eskander; Xiaolin Zi; Bang H Hoang Journal: Sarcoma Date: 2013-02-10