title: Metalloproteinases 2 and 9 activity during promotion and progression stages of rat liver carcinogenesis.
abstract: Activity of metalloproteinases 2 and 9 (MMP-2 and 9) during promotion and progression of rat liver carcinogenesis was investigated in a modified resistant hepatocyte model. Development of preneoplastic liver lesions positive for glutathione S-transferase 7-7-(GST-P 7-7-positive PNL) and tumors besides hepatocytes positive for proliferating cell nuclear antigen (PCNA) were quantified and compared to MMP-2 and-9 activity using gelatin zymography. Marked increases in GST-P 7-7-positive PNL development, PCNA labeling indices, MMP-2 (pro, intermediate and active forms) and pro-MMP-9 activity were observed after proliferative stimulus induced by 2-acetylaminofluorene (2-AAF) exposure cycles. After 2-AAF withdrawal, increase in MMP-2 activity was detected only in neoplastic mixed lesions, whereas active MMP-9 was increased in both PLN and neoplastic tissues. Our findings suggest that MMP-2 may be associated with proliferative events induced by 2-AAF rather than with selective growth of PNL and that MMP-9 could be associated with progression of PNL and neoplastic mixed lesions.
authors.affiliation: School of Medicine, Department of Pathology, UNESP São Paulo State University, Botucatu, SP 18618-000, Brazil.
authors.forename: Kelly Silva
authors.initials: KS
authors.lastname: Furtado
authors.forename: Paulo Wagner
authors.initials: PW
authors.lastname: Pires
authors.forename: Luis Antonio
authors.initials: LA
authors.lastname: Justulin
authors.forename: Maria Aparecida Marchesan
authors.initials: MA
authors.lastname: Rodrigues
authors.forename: Sergio Luis
authors.initials: SL
authors.lastname: Felisbino
authors.forename: Luis Fernando
authors.initials: LF
authors.lastname: Barbisan
mesh_terms: D015073:2-Acetylaminofluorene / Q000633:toxicity; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004052:Diethylnitrosamine / Q000633:toxicity; D018450:Disease Progression; D051549:Glutathione S-Transferase pi / Q000378:metabolism; D007150:Immunohistochemistry; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects; D011230:Precancerous Conditions / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018809:Proliferating Cell Nuclear Antigen; D004052:Diethylnitrosamine; D015073:2-Acetylaminofluorene; D051549:Glutathione S-Transferase pi; C496558:Gstp1 protein, rat; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9