Insulin-like growth factor binding protein-3 induces early apoptosis in malignant prostate cancer cells and inhibits tumor formation in vivo.
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.
Devi
Gayathri R
GR
Department of Pediatrics, School of Medicine, Oregon Health Sciences University, Portland, Oregon, USA. grdevi@avibio.com
Sprenger
Cynthia C
CC
Plymate
Stephen R
SR
Rosenfeld
Ron G
RG
D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects*; D002471:Cell Transformation, Neoplastic; D003470:Culture Media; D018076:DNA, Complementary / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D004847:Epithelial Cells / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000096:biosynthesis* / Q000494:pharmacology*; D008297:Male; D011471:Prostatic Neoplasms / Q000473:pathology*; D014407:Tumor Cells, Cultured
D003470:Culture Media; D018076:DNA, Complementary; D004273:DNA, Neoplasm; D018972:Insulin-Like Growth Factor Binding Protein 3