title: Adenovirus vector-mediated upregulation of spermidine /spermine N1-acetyltransferase impairs human gastric cancer growth in vitro and in vivo.
abstract: Spermidine/spermine N(1)-acetyltransferase (SSAT) is the rate-limiting step in polyamine catabolism. In a previous study, we constructed a recombinant adenovirus, Ad-SSAT, which can express human SSAT. In the present study, we investigated the effect of upregulated and downregulated SSAT on gastric cancer cells. We found that upregulated SSAT could inhibit the growth of MGC803 and SGC7901 cells, whereas adverse results were found with downregulated SSAT. We further analyzed cell cycle profiles and the expression levels of the major cell cycle regulatory proteins of S phase. The results showed that the growth inhibition was caused by S phase arrest. Ad-SSAT suppressed the expression of cyclin A and nuclear factor E2F1 in MGC803 and SGC7901 cells. We observed the E2F promoter activity caused by Ad-SSAT using a reporter gene assay. We also investigated the antitumorigenicity of upregulated SSAT by Ad-SSAT using a SGC7901 xenograft model in nude mice. Our results suggest that the upregulation of SSAT by Ad-SSAT infection inhibited the growth of gastric cancer in vitro and in vivo. Ad-SSAT arrested gastric cancer cells in S phase, which was mediated through downregulation of the cyclin A-E2F signaling pathway.
authors.affiliation: Institute of Biochemistry and Molecular Biology, Shandong University School of Medicine, Jinan, Shandong, 250012, PR China.
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.forename: Hui
authors.initials: H
authors.lastname: Sun
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Yun-Fei
authors.initials: YF
authors.lastname: Yan
authors.forename: Shi-Min
authors.initials: SM
authors.lastname: Chen
authors.forename: Ya-Pei
authors.initials: YP
authors.lastname: Yang
authors.forename: Chun-Xiao
authors.initials: CX
authors.lastname: Xu
authors.forename: Jia-Xuan
authors.initials: JX
authors.lastname: Xin
authors.forename: Xian-Xi
authors.initials: XX
authors.lastname: Liu
mesh_terms: D000123:Acetyltransferases / Q000235:genetics / Q000502:physiology*; D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D015317:Biogenic Polyamines / Q000032:analysis; D045744:Cell Line, Tumor; D019925:Cyclin A / Q000037:antagonists & inhibitors; D050687:E2F1 Transcription Factor / Q000037:antagonists & inhibitors; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D016196:S Phase; D013274:Stomach Neoplasms / Q000737:chemistry / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D015854:Up-Regulation; D000099228:Diamine N-Acetyltransferase
chemical_list: D000123:Acetyltransferases; D015317:Biogenic Polyamines; D019925:Cyclin A; D050687:E2F1 Transcription Factor; D000099228:Diamine N-Acetyltransferase
references.citation: Biochem J. 2006 Feb 15;394(Pt 1):317-24
references.pmid: 16262603
references.citation: J Natl Cancer Inst. 1972 Jan;48(1):165-72
references.pmid: 4652370
references.citation: J Biochem. 2006 Jan;139(1):17-25
references.pmid: 16428315
references.citation: Biochem J. 1990 Sep 15;270(3):615-20
references.pmid: 2241897
references.citation: Nucleic Acids Res. 2005 Sep 22;33(17):5458-70
references.pmid: 16179649
references.citation: J Gene Med. 2006 Aug;8(8):980-9
references.pmid: 16783835
references.citation: Clin Cancer Res. 1999 May;5(5):945-51
references.pmid: 10353725
references.citation: Tumour Biol. 2006;27(5):243-51
references.pmid: 16888408
references.citation: Acta Pharmacol Sin. 2006 Mar;27(3):353-9
references.pmid: 16490173
references.citation: FASEB J. 1993 May;7(8):653-61
references.pmid: 8500690
references.citation: Cell. 1992 Jul 24;70(2):351-64
references.pmid: 1638635
references.citation: Cell. 1994 Jul 15;78(1):161-72
references.pmid: 8033208
references.citation: World J Gastroenterol. 2005 Apr 21;11(15):2244-8
references.pmid: 15818733
references.citation: Cancer Res. 1989 Feb 1;49(3):639-43
references.pmid: 2535963
references.citation: Genes Dev. 1998 Aug 1;12(15):2245-62
references.pmid: 9694791
references.citation: Am J Physiol Endocrinol Metab. 2008 Jun;294(6):E995-1010
references.pmid: 18349109
references.citation: Nucleic Acids Res. 2003 Nov 1;31(21):e127
references.pmid: 14576327
references.citation: Cell Mol Life Sci. 2002 Aug;59(8):1317-26
references.pmid: 12363035
references.citation: J Biol Chem. 2000 Dec 8;275(49):38319-28
references.pmid: 10978316
references.citation: World J Gastroenterol. 2003 Apr;9(4):714-6
references.pmid: 12679917
references.citation: CA Cancer J Clin. 2005 Mar-Apr;55(2):74-108
references.pmid: 15761078
references.citation: Mol Cell Biol. 1992 Dec;12(12):5620-31
references.pmid: 1448092
references.citation: Cancer Res. 2007 Sep 1;67(17):8180-7
references.pmid: 17804731
references.citation: J Biol Chem. 1997 Feb 21;272(8):4904-10
references.pmid: 9030549
references.citation: Cell. 1992 Jul 24;70(2):337-50
references.pmid: 1638634
references.citation: Nat Rev Mol Cell Biol. 2002 Jan;3(1):11-20
references.pmid: 11823794
references.citation: Acta Pharmacol Sin. 2008 May;29(5):606-13
references.pmid: 18430370