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 benign to malignant human prostate epithelial cells in vivo. Further, in a well-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-1R number from 2.0 x 10(4) receptors per cell 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 soft agar in the M12-LISN cells vs the M12 control cells (p < or = 0.01), and a decrease in vivo tumor growth and metastases when injected either subcutaneously or an intraprostatic location (p < or = 0.01). This decrease in tumor volume was not because of a decrease in proliferative capacity, but was associated with an increase in apoptosis in baseline cultures and in response to the apoptotic-inducing agents 6-hydroxyurea, retinoic acid, and transforming growth factor beta 1.
Plymate
S S
SS
Geriatric Research, Education, and Clinical Center, American Lake, VAMC, Tacoma, WA 98493, USA.
Bae
V L
VL
Maddison
L
L
Quinn
L S
LS
Ware
J L
JL
D000818:Animals; D000952:Antigens, Polyomavirus Transforming; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D010641:Phenotype; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000821:virology; D017526:Receptor, IGF Type 1 / Q000235:genetics*; D012842:Sarcoma Virus, Woolly Monkey / Q000737:chemistry*; D014407:Tumor Cells, Cultured
D000952:Antigens, Polyomavirus Transforming; D017526:Receptor, IGF Type 1