Bcl-2 overexpression in melanoma cells increases tumor progression-associated properties and in vivo tumor growth

J Cell Physiol. 2005 Dec;205(3):414-21. doi: 10.1002/jcp.20413.


In this study, we demonstrated that bcl-2 overexpression in human melanoma cells consistently enhanced the activity of multiple metastasis-related proteinases, in vitro cell invasion, and in vivo tumor growth. In particular, by using the M14 parental cell line, the MN8 control clone, and two bcl-2 overexpressing derivatives, we found that bcl-2 overexpressing cells exposed to hypoxia, when compared to parental cells, expressed higher level of several metalloproteases (MMPs) such as MMP-2, MMP-7, MT1-MMP, and tissue inhibitors of metalloproteases-1 and -2. Moreover, bcl-2 overexpression in melanoma cells enhanced in vitro invasion on matrigel and, in vivo tumor growth. The more aggressive behavior of bcl-2 transfectants tumors is significantly associated to an increase in MMP-2 expression as well as in a more elevated microvessel density as compared to the parental line. Taken together, our data suggest that bcl-2 plays a pivotal role in the regulation of molecules associated with the migratory and invasive phenotype, contributing, in cooperation to hypoxia, to tumor progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Biocompatible Materials
  • Cell Division
  • Cell Hypoxia
  • Cell Line, Tumor
  • Collagen
  • Disease Progression
  • Drug Combinations
  • Female
  • Humans
  • Immunohistochemistry
  • Integrins / metabolism
  • Laminin
  • Matrix Metalloproteinases / metabolism
  • Melanoma / metabolism*
  • Melanoma / pathology*
  • Mice
  • Mice, Nude
  • Neoplasm Invasiveness
  • Neoplasm Transplantation
  • Proteoglycans
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Tissue Inhibitor of Metalloproteinases / metabolism
  • Transplantation, Heterologous


  • Biocompatible Materials
  • Drug Combinations
  • Integrins
  • Laminin
  • Proteoglycans
  • Proto-Oncogene Proteins c-bcl-2
  • Tissue Inhibitor of Metalloproteinases
  • matrigel
  • Collagen
  • Matrix Metalloproteinases