Metalloproteinases 2 and -9 activity during promotion and progression stages of rat liver carcinogenesis |
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Authors: | Kelly Silva Furtado Paulo Wagner Pires Jr" target="_blank">Luis Antonio JustulinJr Maria Aparecida Marchesan Rodrigues Sergio Luis Felisbino Luis Fernando Barbisan |
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Institution: | 1.School of Medicine, Department of Pathology,UNESP S?o Paulo State University,Botucatu,Brazil;2.Department of Cell Biology, Institute of Cell Biology,UNICAMP,Campinas,Brazil;3.Department of Morphology, Institute of Biosciences,UNESP S?o Paulo State University,Botucatu,Brazil |
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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. |
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Keywords: | Rat liver carcinogenesis Resistant hepatocyte model Metalloproteinases Preneoplastic and neoplastic lesions |
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