Insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1) is a potential tumor suppressor protein for prostate cancer

Insulin-like growth factor binding protein-related protein-1 (IGFBP-rP1) ha s been shown to have decreased expression in the progression from benign to malignant prostate epithelial cells (V, Hwa et al,, J, Clin Endocrinol, Me tab., 83: 4355-4362, 1998). The present study was undertaken to determine t he effects of the re-expression of IGFBP-rP1 in a cell line from a model of human prostate cancer, M12, in which IGFBP-rP1 expression had been demonst rated to decrease from the parent epithelial cell, P69, to the malignant su bline, M12, An IGFBP-rP1 cDNA encoding the protein was transfected into M12 cells in a plasmid that resulted in constitutive-expression of IGFBP-rP1, Clones of transfected M12 cells were selected for low (L) and high (H) leve ls of expression, and the plasmid vector alone was transfected into M12 as a control. After transfection, there was a marked alteration in the morphol ogy of the M12 cells such that the H clones had an elongated appearance whe n compared with the M12 control cells. The M12 clones overexpressing IGFBP- rP1 had a dose-related increase in population doubling time, decreased colo ny formation in soft agar, an increased propensity to undergo apoptosis in response to 6-hydroxyurea, and decreased tumor formation in male athymic, n ude mice, These data suggest that IGFBP-rP1 may have a suppressive effect o n prostate cancer development.