title: Overexpression of Ras homologous C (RhoC) induces malignant transformation of hepatocytes in vitro and in nude mouse xenografts.
abstract: Ras homologous C (RhoC) is expressed in various cancers, including hepatocellular carcinoma (HCC). In this study, we first analyzed RhoC expression in 46 HCC tissue specimens and found that RhoC expression was significantly increased in HCC tissues compared to the adjacent normal liver tissues. Next, we investigated the role of RhoC in malignant transformation of normal hepatocytes. The HL7702 cell line was stably transfected with a RhoC expression vector and then subjected to cell proliferation, differentiation, colony formation, migration and invasion assays, as well as nude mouse xenograft assays. Gene expressions in these cells were determined using RT-PCR and Western blot. Overexpression of RhoC significantly promoted proliferation and anchorage-independent growth of HL7702 cells, but suppressed cell differentiation, as compared with the parental cells and the empty vector-transfected control cells. Moreover, RhoC overexpression induced migration and invasion of HL7702 cells in vitro. Molecularly, RhoC increased the expression of cell cycle-related genes, matrix metalloprotease 2 (MMP2), MMP9 and vascular endothelial growth factor (VEGF). In addition, RhoC-transfected cells formed tumors in nude mice, whereas vector-transfected HL7702 cells did not form any tumors in nude mice. This study demonstrated the role of RhoC overexpression in malignant transformation of normal human hepatocytes, suggesting that RhoC may function as an oncogene in hepatocytes.
authors: Department of General Surgery, the First Hospital of Jilin University, Changchun, Jilin, China.
authors: Shuli
authors: S
authors: Xie
authors: Mingguang
authors: M
authors: Zhu
authors: Guoyue
authors: G
authors: Lv
authors: Yajun
authors: Y
authors: Geng
authors: Guofu
authors: G
authors: Chen
authors: Jian
authors: J
authors: Ma
authors: Guangyi
authors: G
authors: Wang
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D015870:Gene Expression; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D014183:Transplantation, Heterologous; D014410:Tumor Stem Cell Assay; D020741:rho GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D000075024:rhoC GTP-Binding Protein
chemical_list: C066690:RHOC protein, human; D020741:rho GTP-Binding Proteins; D000075024:rhoC GTP-Binding Protein
references: Oncogene. 2010 Sep 9;29(36):4989-5005
references: 20639898
references: Cancer Res. 2010 Feb 1;70(3):863-7
references: 20103650
references: Am J Pathol. 2002 Feb;160(2):579-84
references: 11839578
references: Cancer Res. 2008 Sep 15;68(18):7613-20
references: 18794150
references: Methods Enzymol. 2006;407:637-47
references: 16757358
references: Mol Ther. 2005 Feb;11(2):267-74
references: 15668138
references: BMC Res Notes. 2009 Jul 17;2:140
references: 19615042
references: Curr Opin Genet Dev. 2002 Feb;12(1):36-43
references: 11790552
references: J Biol Chem. 2011 Jan 28;286(4):3139-48
references: 21087931
references: World J Gastroenterol. 2007 Jul 7;13(25):3517-22
references: 17659701
references: Eur J Cancer. 2006 Jul;42(10):1455-65
references: 16750623
references: Cell Cycle. 2010 Jun 15;9(12):2456-63
references: 20603602
references: Eur J Neurosci. 2007 Nov;26(10):2979-88
references: 18001292
references: World J Gastroenterol. 2003 Sep;9(9):1950-3
references: 12970882
references: Semin Cancer Biol. 2001 Apr;11(2):167-73
references: 11322835
references: J Cell Biol. 2011 May 16;193(4):655-65
references: 21576392
references: Lab Invest. 2003 Jun;83(6):861-70
references: 12808121
references: Clin Cancer Res. 1999 Sep;5(9):2511-9
references: 10499627
references: Cell Cycle. 2009 Nov 1;8(21):3592-600
references: 19823025
references: J Clin Gastroenterol. 2010 Apr;44(4):239-45
references: 20216082
references: J Invest Dermatol. 2006 Apr;126(4):862-8
references: 16470169
references: J Viral Hepat. 2004 Sep;11(5):383-93
references: 15357643
references: FEBS Lett. 2008 Jun 18;582(14):2093-101
references: 18460342
references: J Epidemiol. 2011;21(6):401-16
references: 22041528
references: Nature. 2000 Aug 3;406(6795):532-5
references: 10952316
references: Gynecol Oncol. 2011 May 1;121(2):395-401
references: 21310472
references: Br J Cancer. 1998;77(1):147-52
references: 9459160
references: Biochim Biophys Acta. 2009 Dec;1796(2):91-8
references: 19327386
references: Nat Genet. 2002 Aug;31(4):339-46
references: 12149612
references: Oncogene. 2010 Apr 22;29(16):2441-8
references: 20101212
references: Bioessays. 2005 Jun;27(6):602-13
references: 15892119
references: J Mol Med (Berl). 2007 Oct;85(10):1149-56
references: 17549441
references: Med Oncol. 2012 Sep;29(3):1802-9
references: 21674277
references: Laryngoscope. 2001 Jul;111(7):1285-9
references: 11568556
references: Cell Signal. 2003 Mar;15(3):327-38
references: 12531431
references: Cancer Res. 2001 Mar 1;61(5):2129-37
references: 11280777
references: Biochim Biophys Acta. 2012 Jan;1825(1):29-36
references: 22020293
references: J Gastrointest Surg. 2003 Nov;7(7):884-9
references: 14592662
references: Curr Drug Targets. 2011 Jul 1;12(8):1194-201
references: 21561416
references: Genes Dev. 2005 Sep 1;19(17):1974-9
references: 16107613
references: Acta Pharmacol Sin. 2010 Sep;31(9):1165-71
references: 20676120