Journal of Molecular Histology

, Volume 40, Issue 1, pp 1–11 | Cite as

Metalloproteinases 2 and -9 activity during promotion and progression stages of rat liver carcinogenesis

  • Kelly Silva Furtado
  • Paulo Wagner Pires
  • Luis Antonio JustulinJr.
  • Maria Aparecida Marchesan Rodrigues
  • Sergio Luis Felisbino
  • Luis Fernando Barbisan
Original Paper


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.


Rat liver carcinogenesis Resistant hepatocyte model Metalloproteinases Preneoplastic and neoplastic lesions 



This work was supported by CAPES, FAPESP and TOXICAM. Kelly S. Furtado was recipient of a fellowship from CAPES.


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Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • Kelly Silva Furtado
    • 1
    • 3
  • Paulo Wagner Pires
    • 2
  • Luis Antonio JustulinJr.
    • 3
  • Maria Aparecida Marchesan Rodrigues
    • 1
  • Sergio Luis Felisbino
    • 3
  • Luis Fernando Barbisan
    • 3
  1. 1.School of Medicine, Department of PathologyUNESP São Paulo State UniversityBotucatuBrazil
  2. 2.Department of Cell Biology, Institute of Cell BiologyUNICAMPCampinasBrazil
  3. 3.Department of Morphology, Institute of BiosciencesUNESP São Paulo State UniversityBotucatuBrazil

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