TYPE-1 INSULIN-LIKE-GROWTH-FACTOR RECEPTOR REEXPRESSION IN THE MALIGNANT PHENOTYPE OF SV40-T-IMMORTALIZED HUMAN PROSTATE EPITHELIAL-CELLS ENHANCES APOPTOSIS

The authors have previously shown that the type 1 insulin-like growth factor receptor (IGF-1R) is decreased in the transformation from benig n to malignant human prostate epithelial cells in vivo, Further, in a welt-described human SV40-T immortalized human epithelial cell system beginning with the immortalized, but rarely tumorigenic P69SV40-T cell line, to the highly tumorigenic and metastatic M12 subline, there is a similar decrease in IGF-1 R number from 2.0 x 10(4) receptors per ce ll to 1.1 x 10(3) receptors per cell, When the IGF-1R was reexpressed in the M12 subline using a retroviral expression vector, M12-LISN, to a receptor number similar to that of the P69SV40-T parental cell line, the authors demonstrated a marked decrease in colony formation in sof t agar in the M12-LISN cells vs the M12 control cells (p less than or equal to 0.01), and a decrease in vivo tumor growth and metastases whe n injected either subcutaneously or an intraprostatic location (p less than or equal to 0.01). This decrease in tumor volume was not because of a decrease in proliferative capacity, but was associated with an i ncrease in apoptosis in baseline cultures and in response to the apopt otic-inducing agents 6-hydroxyurea, retinoic acid, and transforming gr owth factor beta(1).