title: Expression of glutathione peroxidase 2 is associated with not only early hepatocarcinogenesis but also late stage metastasis.
abstract: Understanding of mechanisms of cancer progression is very important for reduction of cancer mortality. Of six rat hepatocellular carcinoma (HCC) cell lines, differing in their metastatic potential to the lung after inoculation into the tail vein of nude mice, the most metastatic featured particular overexpression of glutathione peroxidase 2 (GPX2). Therefore, we analyzed the influence of interference in highly metastatic L2 cells by siRNA transfection. Gpx2 siRNA significantly inhibited cell proliferation at 24 and 48h time points with induction of apoptosis but not cell cycle arrest. High expression of mutated p53 was detected in all HCC cell lines, with reduction in Gpx2 siRNA-transfected cells. Migration and invasion in vitro were also suppressed as compared to control siRNA-transfected cells and secretion of matrix metalloproteinase 9 was reduced. In vivo, the numbers and areas of metastatic nodules per area in the lungs were significantly reduced in the mice inoculated with Gpx2 siRNA-transfected cells as compared to control siRNA-transfected cells. In conclusion, expression of GPX2 is associated with cancer metastasis from rat HCCs both in vitro and in vivo. Together with immunohistochemical findings of elevated expression in rat and also human liver lesions, the results point to important roles in hepatocarcinogenesis.
authors.affiliation: Department of Experimental Pathology, Graduate School of Medicine, Nagoya City University, Nagoya, Japan. shugo@med.nagoya-cu.ac.jp
authors.forename: Shugo
authors.initials: S
authors.lastname: Suzuki
authors.forename: Pornsiri
authors.initials: P
authors.lastname: Pitchakarn
authors.forename: Kumiko
authors.initials: K
authors.lastname: Ogawa
authors.forename: Aya
authors.initials: A
authors.lastname: Naiki-Ito
authors.forename: Teera
authors.initials: T
authors.lastname: Chewonarin
authors.forename: Wanisa
authors.initials: W
authors.lastname: Punfa
authors.forename: Makoto
authors.initials: M
authors.lastname: Asamoto
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Shirai
authors.forename: Satoru
authors.initials: S
authors.lastname: Takahashi
mesh_terms: D000368:Aged; D000818:Animals; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D020868:Gene Silencing; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D008175:Lung Neoplasms / Q000378:metabolism / Q000556:secondary; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; C117436:GPX2 protein, human; D005979:Glutathione Peroxidase; C525844:glutathione peroxidase 2, rat; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat
keywords: Cancer progression; Carcinogenesis; Glutathione peroxidase 2; Hepatocellular carcinoma; Metastasis