K. Degeest et al., DIFFERENTIAL RESPONSE OF CERVICAL INTRAEPITHELIAL AND CERVICAL-CARCINOMA CELL-LINES TO TRANSFORMING GROWTH-FACTOR-BETA-1, Gynecologic oncology, 55(3), 1994, pp. 376-385
Transforming growth factor-beta 1 (TGF-beta 1) is a potent inhibitor o
f epithelial cell proliferation. It has been proposed that loss of sen
sitivity to growth inhibition by TGF-beta 1 may be an important step i
n the development of cervical carcinoma, but it remains unclear whethe
r this represents an early or a late event. We compared the sensitivit
y to TGF-beta 1 of nontumorigenic human papillomavirus deoxyribonuclei
c acid (HPV DNA)-positive cell lines derived from cervical intraepithe
lial neoplasia (CIN), of newly established cervical carcinoma cell lin
es, of nontumorigenic HPV DNA-transfected cervical cell lines, and of
normal ectocervical cells. There is a dose-dependent inhibition of DNA
synthesis by TGF-beta 1 in the CIN cell lines and the HPV DNA-transfe
cted cell lines. The carcinoma cell lines are resistant to the growth
inhibitory effects of TGF-beta 1. The CIN cell lines are significantly
more sensitive than the carcinoma cell lines (P < 0.001), but signifi
cantly less sensitive than normal cervical cells (P < 0.05). A CIN cel
l line which contains HPV 31b DNA is more sensitive to TGF-beta 1 at e
arly passage than at late passage (P < 0.05). There are no differences
in the sensitivity to the growth inhibitory effects of TGF-beta 1 bet
ween subclones of this cell line that have different episomal HPV DNA
content, population-doubling time, or differentiation characteristics.
Both normal and abnormal cervical epithelial cells were able to secre
te latent TGF-beta 1 or TGF-beta 2. We conclude that resistance to gro
wth inhibition by TGF-beta 1 is likely to be a late event in the devel
opment of cervical carcinoma; it is not the mere consequence of immort
alization by HPV genes acquired following transfection in vitro or inf
ection in vivo. (C) 1994 Academic Press, Inc.