TYPE-1 INSULIN-LIKE-GROWTH-FACTOR RECEPTOR REEXPRESSION IN THE MALIGNANT PHENOTYPE OF SV40-T-IMMORTALIZED HUMAN PROSTATE EPITHELIAL-CELLS ENHANCES APOPTOSIS
Ssr. Plymate et al., TYPE-1 INSULIN-LIKE-GROWTH-FACTOR RECEPTOR REEXPRESSION IN THE MALIGNANT PHENOTYPE OF SV40-T-IMMORTALIZED HUMAN PROSTATE EPITHELIAL-CELLS ENHANCES APOPTOSIS, ENDOCRINE, 7(1), 1997, pp. 119-124
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).