title: Regulation of human hepatocellular carcinoma cells by Spred2 and correlative studies on its mechanism.
abstract: Members of the Spred gene family are negative regulators of the Ras/Raf-1/ERK pathway, which has been associated with several features of the tumor malignancy. However, the effect of Spred genes on hepatocellular carcinoma (HCC) remains uninvestigated. In the present work, we analyzed the in vitro and in vivo effects of Spred2 expression on the hepatic carcinoma cell line, SMMC-7721. In addition to attenuated ERK activation, which inhibited the proliferation and migration of unstimulated and HGF-stimulated SMMC-7721 cells. Adenovirus-mediated Spred2 overexpression induced the activation of caspase-3 and apoptosis, as well as reduced the expression level of Mcl-1. Most importantly, the knockdown of Spred2 markedly enhanced tumor growth in vivo. In conclusion, these results suggest that Spred2 could qualify as a potential therapeutic target in HCC.
authors.affiliation: Lanzhou University of Technology, Lanzhou 730050, PR China.
authors.forename: Xiao-Ni
authors.initials: XN
authors.lastname: Ma
authors.forename: Xiao-Yun
authors.initials: XY
authors.lastname: Liu
authors.forename: Yue-Feng
authors.initials: YF
authors.lastname: Yang
authors.forename: Feng-Jun
authors.initials: FJ
authors.lastname: Xiao
authors.forename: Qing-Fang
authors.initials: QF
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Yan
authors.forename: Qun-Wei
authors.initials: QW
authors.lastname: Zhang
authors.forename: Li-Sheng
authors.initials: LS
authors.lastname: Wang
authors.forename: Xue-Yan
authors.initials: XY
authors.lastname: Li
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015536:Down-Regulation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology*; D051379:Mice; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics*
chemical_list: C579094:Mcl1 protein, mouse; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D012097:Repressor Proteins; C500760:SPRED2 protein, human; D048049:Extracellular Signal-Regulated MAP Kinases