TY - JOUR
T1 - Metalloproteinases 2 and -9 activity during promotion and progression stages of rat liver carcinogenesis
AU - Furtado, Kelly Silva
AU - Pires, Paulo Wagner
AU - Justulin, Luis Antonio
AU - Rodrigues, Maria Aparecida Marchesan
AU - Felisbino, Sergio Luis
AU - Barbisan, Luis Fernando
N1 - Funding Information:
Acknowledgments This work was supported by CAPES, FAPESP and TOXICAM. Kelly S. Furtado was recipient of a fellowship from CAPES.
PY - 2009/2
Y1 - 2009/2
N2 - 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.
AB - 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.
KW - Metalloproteinases
KW - Preneoplastic and neoplastic lesions
KW - Rat liver carcinogenesis
KW - Resistant hepatocyte model
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U2 - 10.1007/s10735-008-9206-x
DO - 10.1007/s10735-008-9206-x
M3 - Article
C2 - 19052882
AN - SCOPUS:67749097715
SN - 1567-2379
VL - 40
SP - 1
EP - 11
JO - Journal of Molecular Histology
JF - Journal of Molecular Histology
IS - 1
ER -