REEXPRESSION OF THE TYPE-1 INSULIN-LIKE GROWTH-FACTOR RECEPTOR INHIBITS THE MALIGNANT PHENOTYPE OF SIMIAN-VIRUS-40 T-ANTIGEN IMMORTALIZED HUMAN PROSTATE EPITHELIAL-CELLS
Sr. Plymate et al., REEXPRESSION OF THE TYPE-1 INSULIN-LIKE GROWTH-FACTOR RECEPTOR INHIBITS THE MALIGNANT PHENOTYPE OF SIMIAN-VIRUS-40 T-ANTIGEN IMMORTALIZED HUMAN PROSTATE EPITHELIAL-CELLS, Endocrinology, 138(4), 1997, pp. 1728-1735
Type 1 insulin-like growth factor receptor (IGF-IR) expression is decr
eased in prostate cancer compared to that in noncancerous prostate epi
thelium. We have demonstrated that as the simian virus 40 T antigen(SV
40T) immortalized human prostate epithelial cell line, P69SV40T, under
goes transformation from a poorly tumorigenic to a malignant phenotype
, the M12 subline, there is a significant decrease in IGF-1R expressio
n. In the present study, we examine the effects of reexpression of the
IGF-1R on the malignant phenotype of M12 cells. The IGF-1R was reexpr
essed in M12 cells using a retroviral vector containing a 7-kilobase c
oding sequence for the IGF-1R, LISN, to create several clones of the M
12-LISN cell line. As a control, M12 cells were also infected with a r
etroviral vector (LNL6) without the 7-kilobase IGF-1R insert (M12-LNL6
clones. Functional assays were performed with two separate clones eac
h of M12-LNLG and M12-LISN cells. Each clone of M12-LISN cells regaine
d the proliferative response to IGF that was lost in the transition fr
om P69SV40T cells to M12 cells. In addition, M12-LISN clones had a sig
nificantly decreased growth rate compared to the M12-LNL6 cells when i
njected sc in athymic/nude mice (P < 0.001). Tumorigenicity, as assess
ed by anchorage-independent growth of colonies in soft agar, was also
decreased by 75% in the M12-LISN clones compared to that in the M12-LN
L6 control cells. These data demonstrate that reexpression of the IGF-
IR in a malignant human prostate epithelial cell line results in decre
ased tumor growth and decreased anchorage-independent colony formation
independent of an increased proliferative response to IGF. Reexpressi
on of the IGF-1R may be associated with reacquisition of the regulatio
n of cellular proliferative and differentiation functions mediated by
the IGF-1R that ar e lost as prostate epithelial cells undergo convers
ion to a malignant phenotype.