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

Gayathri R. Devi, Cynthia C. Sprenger, Stephen R. Plymate, Ron G. Rosenfeld

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)141-152
Number of pages12
JournalProstate
Volume51
Issue number2
DOIs
StatePublished - May 1 2002

Keywords

  • Insulin-like growth factor
  • M12 prostate epithelial cells
  • Tumor suppressor

ASJC Scopus subject areas

  • Oncology
  • Urology

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