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  • N-Myc and Bcl-2 coexpression induces MMP-2 secretion and activation in human neuroblastoma cells.

N-Myc and Bcl-2 coexpression induces MMP-2 secretion and activation in human neuroblastoma cells.

Oncogene (2002-06-27)
Daniel Noujaim, Cynthia M van Golen, Kenneth L van Golen, Alyssa Grauman, Eva L Feldman
ABSTRACT

Neuroblastoma is a peripheral nervous system tumor that accounts for 8-10% of all solid childhood tumors. N-Myc is the most reliable prognostic indicator for neuroblastoma. Bcl-2 is detected in 40-60% of primary neuroblastoma tumors and demonstrates anti-apoptotic action by conferring resistance to chemotherapy and radiation treatment. In neuroblastoma cell lines, the coexpression of N-Myc and Bcl-2 leads to increased tumorigenic properties. Matrix metalloproteinases (MMPs) are endopeptidases that degrade a wide range of basement membrane components, a process important for tumor invasion. This study investigates the effect of N-Myc and Bcl-2 on MMP expression and activation. MMP-2 expression and secretion are increased in SHEP neuroblastoma cells expressing Bcl-2 alone (SHEP/Bcl-2 cells) or both N-Myc and Bcl-2 (SHEP/N-Myc/Bcl-2 cells). MMP-2 activity is increased in the SHEP/N-Myc/Bcl-2 cells yet remains unchanged in SHEP/Bcl-2 cells. TIMP-2 expression is high in SHEP/Bcl-2 cells, which likely inhibits MMP-2 activity, and absent in SHEP/N-Myc/Bcl-2 cells, allowing MMP-2 activity. Invasion is increased in SHEP/N-Myc/Bcl-2 cells and prevented by the use of a pharmacologic MMP-2 inhibitor. These data imply that N-Myc and Bcl-2 cooperate to increase the expression, secretion, and activation of MMP-2, which likely leads to a more tumorigenic phenotype due to increased MMP-2 mediated invasion.

MATERIALS
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Sigma-Aldrich
QCM ECMatrix Cell Invasion Assay, 24-well (8 µm), colorimetric, The CHEMICON Cell Invasion Assay Kit uses a 24-well plate, with 8 um pores, which provides an efficient system for evaluating the invasion of tumor cells through a basement membrane model.
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100 μL
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