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

AbstractBACKGROUND:
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.
AuthorsGayathri R Devi, Cynthia C Sprenger, Stephen R Plymate, Ron G Rosenfeld
JournalThe Prostate (Prostate) Vol. 51 Issue 2 Pg. 141-52 (May 01 2002) ISSN: 0270-4137 [Print] United States
PMID11948969 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
CopyrightCopyright 2002 Wiley-Liss, Inc.
Chemical References
  • Culture Media
  • DNA, Complementary
  • DNA, Neoplasm
  • Insulin-Like Growth Factor Binding Protein 3
Topics
  • Apoptosis (drug effects)
  • Blotting, Western
  • Cell Division (drug effects)
  • Cell Transformation, Neoplastic
  • Culture Media
  • DNA, Complementary (genetics)
  • DNA, Neoplasm (genetics)
  • Electrophoresis, Polyacrylamide Gel
  • Epithelial Cells (physiology)
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Insulin-Like Growth Factor Binding Protein 3 (biosynthesis, pharmacology)
  • Male
  • Prostatic Neoplasms (pathology)
  • Tumor Cells, Cultured

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