Insulin-like growth factor binding protein-3 induces early apoptosis in malignant prostate cancer cells and inhibits tumor formation in vivo.

Journal Article (Journal Article)

BACKGROUND: Insulin-like growth factor binding protein (IGFBP-3) levels are significantly reduced in malignant prostate epithelial cells. In this study, we evaluated the role of endogenous IGFBP-3 on prostate cancer cell growth and tumorigenesis. METHODS: IGFBP-3 was re-expressed by stable transfection of human IGFBP-3 cDNA in a model of human prostate cancer, M12, a malignant subline in which IGFBP-3 levels are undetectable in comparison to the parent epithelial cell, P69. Effect of IGFBP-3 re-expression (M12-BP-3) on growth kinetics, morphology, propensity to apoptosis, and in vivo tumor formation were studied. RESULTS: M12-BP-3 cells secreted IGFBP-3 and growth arrested at a cell density that was threefold lower than control cells and this was associated with marked alteration in cell morphology. Control cells when grown in conditioned media secreted by M12-BP-3 also showed altered morphology compared to when cultured in IGFBP-3-immunodepleted conditioned media. The M12-BP-3 clones showed altered mitochondrial membrane potential, increased PARP cleavage, increase in sub-G1 peak, decreased levels of neuron specific enolase, and decreased tumor formation in athymic, nude mice. CONCLUSIONS: These data suggest that IGFBP-3 induces early apoptosis and has potential tumor suppressive effect in prostate cancer. Prostate 51: 141-152, 2002.

Full Text

Duke Authors

Cited Authors

  • Devi, GR; Sprenger, CC; Plymate, SR; Rosenfeld, RG

Published Date

  • May 1, 2002

Published In

Volume / Issue

  • 51 / 2

Start / End Page

  • 141 - 152

PubMed ID

  • 11948969

International Standard Serial Number (ISSN)

  • 0270-4137

Digital Object Identifier (DOI)

  • 10.1002/pros.10068


  • eng

Conference Location

  • United States