INTS6/DICE1 inhibits growth of human androgen-independent prostate cancer cells by altering the cell cycle profile and Wnt signaling
Tóm tắt
The gene encoding integrator complex subunit 6 (INTS6), previously known as deleted in cancer cells 1 (DICE1, OMIM 604331) was found to be frequently affected by allelic deletion and promoter hypermethylation in prostate cancer specimens and cell lines. A missense mutation has been detected in prostate cancer cell line LNCaP. Together, these results suggest INTS6/DICE1 as a putative tumor suppressor gene in prostate cancer. In this study, we examined the growth inhibitory effects of INTS6/DICE1 on prostate cancer cells. Markedly decreased INTS6/DICE1 mRNA levels were detected in prostate cancer cell lines LNCaP, DU145 and PC3 as well as CPTX1532 as compared to a cell line derived from normal prostate tissue, NPTX1532. Exogenous re-expression of INTS6/DICE1 cDNA in androgen-independent PC3 and DU145 cell lines substantially suppressed their ability to form colonies in vitro. This growth inhibition was not due to immediate induction of apoptosis. Rather, prostate cancer cells arrested in G1 phase of the cell cycle. Expression profiling of members of the Wnt signaling pathway revealed up-regulation of several genes including disheveled inhibitor CXXC finger 4 (CXXC4), frizzled homologue 7 (FZD7), transcription factor 7-like 1 (TCF7L1), and down-regulation of cyclin D1. These results show for the first time a link between INTS6/DICE1 function, cell cycle regulation and cell-cell communication involving members of the Wnt signaling pathway.
Tài liệu tham khảo
Pienta KJ, Bradley D: Mechanisms underlying the development of andogen independent prostate cancer. Clin Cancer Res. 2006, 12: 1665-1671. 10.1158/1078-0432.CCR-06-0067.
Wieland I, Arden KC, Michels D, Klein-Hitpass L, Böhm M, Viars CS, Weidle UH: Isolation of DICE1: A gene frequently affected by LOH and down-regulated in lung carcinomas. Oncogene. 1999, 18: 4530-4537. 10.1038/sj.onc.1202806.
Wieland I, Röpke A, Stumm M, Sell C, Weidle UH, Wieacker PF: Molecular characterization of the DICE1 (DDX26) tumor suppressor gene in lung carcinoma cells. Oncol Res. 2001, 12: 491-500.
Li WJ, Hu N, Su H, Wang C, Goldstein AM, Wang Y, Emmert-Buck MR, Roth MJ, Guo WJ, Taylor PR: Allelic loss on chromosome 13q14 and mutation in deleted in cancer 1 gene in esophageal squamous cell carcinoma. Oncogene. 2003, 22: 314-318. 10.1038/sj.onc.1206098.
Röpke A, Buhtz P, Böhm M, Seger J, Wieland I, Allhoff EP, Wieacker PF: Promoter CpG hypermethylation and down-regulation of DICE1 expression in prostate cancer. Oncogene. 2005, 24: 6667-6675. 10.1038/sj.onc.1208824.
Hernández M, Papadopoulos N, Almeida TA: Absence of mutations in DICE1/DDX26 gene in human cancer cell lines with frequent 13q14 deletions. Cancer Genet Cytogenet. 2005, 163: 91-92. 10.1016/j.cancergencyto.2005.04.014.
Cancer Genome Project as of 06/2009. [http://www.sanger.ac.uk]
Whittaker CA, Hynes RO: Distribution and evolution of von Willebrand/Integrin A domains: Widely dispersed domains with roles in cell adhesion and elsewhere. Mol Biol Cell. 2002, 13: 3369-3387. 10.1091/mbc.E02-05-0259.
Baillat D, Hakimi M-A, Näär AM, Shilatifard A, Cooch N, Shiekhatter R: Integrator, a multiprotein mediator of small nuclear RNA processing, associates with the C-terminal repeat of RNA polymerase II. Cell. 2005, 123: 265-276. 10.1016/j.cell.2005.08.019.
Zhang Y, Liu T, Yan P, Huang T, DeWille J: Identification and characterization of CCAAT enhancer binding proteindelta (C/EBPdelta) target genes in G0 growth arrested mammary epithelial cells. BMC Mol Biol. 2008, 9: 83-10.1186/1471-2199-9-83.
Rozenblatt-Rosen O, Nagaike T, Francis JM, Kaneko S, Glatt KA, Hughes CM, LaFramboise T, Manley JL, Meyerson M: The tumor suppressor Cdc73 functionally associates with CPSF and CstF 3' mRNA processing factors. Proc Natl Acad Sci USA. 2009, 106: 755-760. 10.1073/pnas.0812023106.
Hoff HB, Tresini M, Li S, Sell C: DBI-1, a novel gene related to the Notch family, modulates mitogenic response to insulin-like growth factor 1. Exp Cell Res. 1998, 238: 359-370. 10.1006/excr.1997.3865.
Wieland I, Sell C, Weidle UH, Wieacker P: Ectopic expression of DICE1 suppresses tumor cell growth. Oncol Rep. 2004, 12: 207-211.
Bright RK, Vocke CD, Emmert-Buck MR, Duray PH, Solomon D, Fetsch P, Rhim JS, Linehan WM, Topalian SL: Generation and genetic characterization of immortal human prostate epithelial cell lines derived from primary cancer specimens. Cancer Res. 1997, 57: 995-1002.
Zi X, Simoneau AR, Hope C, Xie J, Holcombe RF, Hoang BH: Expression of Frzb/secreted frizzled-related protein 3, a secreted Wnt antagonist, in human androgen-independent prostate cancer PC-3 cells suppresses tumor growth and cellular invasiveness. Cancer Res. 2005, 65: 9762-9770. 10.1158/0008-5472.CAN-05-0103.
Hongo A, D'Ambrosio C, Miura M, Morrione A, Baserga R: Mutational analysis of the mitogenic and transforming activities of the insulin-like growth factor I receptor. Oncogene. 1996, 12: 1231-1238.
O'Connor R, Kaufmann-Zeh A, Liu Y, Lehar S, Evan GI, Baserga R: Identification of domains of the insulin-like growth factor I receptor that are required for protection from apoptosis. Mol Cell Biol. 1997, 17: 427-435.
Brodt P, Fallavollita L, Khatib A-M, Samani AA, Zhang D: Cooperative regulation of the invasive and metastatic phenotypes by different domains of the type I insulin-like growth factor receptor β subunit. J Biol Chem. 2001, 276: 33608-33615. 10.1074/jbc.M102754200.
Grzmil M, Hemmerlein B, Thelen P, Schweyer S, Burfeind P: Blockade of the type I IGF receptor expression in human prostate cancer cells inhibits proliferation and invasion, up-regulates IGF binding protein-3, and suppresses MMP-2 expression. J Pathol. 2004, 202: 50-59. 10.1002/path.1492.
Morali OG, Delmas V, Moore R, Jeanny C, Thiery JP, Larue L: IGF-II induces rapid β-catenin relocation to the nucleus during epithelium to mesenchyme transition. Oncogene. 2001, 20: 4942-4950. 10.1038/sj.onc.1204660.
Zhao H, Cui Y, Dupont J, Sun H, Hennighausen L, Yakar S: Overexpression of the tumor suppressor gene phosphatase and tensin homologue partially inhibits Wnt-1-induced mammary tumorigenesis. Cancer Res. 2005, 65: 6864-6873. 10.1158/0008-5472.CAN-05-0181.
Hino SI, Kishida S, Michiue T, Fukui A, Sakamoto I, Takada S, Asashima M, Kikuchi A: Inhibition of the Wnt signaling pathway by Idax, a novel Dvl-binding protein. Mol Cell Biol. 2001, 21: 330-342. 10.1128/MCB.21.1.330-342.2001.
Pear WS, Nolan GP, Scott ML, Baltimore D: Production of high-titer helper-free retroviruses by transient transfection. Proc Natl Acad Sci USA. 1993, 90: 8392-8396. 10.1073/pnas.90.18.8392.
Chomczynski P, Sacchi N: Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987, 162: 156-159. 10.1016/0003-2697(87)90021-2.
Harlow E, Lane D: Antibodies: A Laboratory Manual. 1988, Cold Spring Harbor, Cold Spring Harbor Laboratory Press
Drewniok C, Wienrich BG, Schön M, Ulrich J, Zen Q, Telen MJ, Hartig RJ, Wieland I, Gollnick H, Schön MP: Molecular interactions of B-CAM (Basal-Cell Adhesion Molecule) and laminin in epithelial skin cancer. Arch Dermatol Res. 2004, 296: 59-66. 10.1007/s00403-004-0481-4.
Livak KJ, Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT Method. Methods. 2001, 25: 402-408. 10.1006/meth.2001.1262.