Expression and action of parathyroid hormone related peptide (
pthrp) in human cervical epithelial cells at different stages of
differentiation.
Kremer, Richard, Craig D. Woodworth, and David Goltzman.
Calcium Research Laboratories, Royal Victoria Hospital, and
Department of Medicine, McGill University, Montreal, Quebec, Canada,
H3A 1A1, Laboratory of Biology, National Cancer Institute, Bethesda,
Maryland 20892, USA
APStracts 3:0063C, 1996.
Parathyroid hormone-related peptide (PTHRP) expression and activity
were analyzed in normal human ectocervical keratinocytes (HCX) and
keratinocytes immortalized by transfection with human papillomavirus
(HPV) type 16 and 18 DNAs. In normal cells trans-retinoic acid (RA)
and 2.0 mM calcium significantly stimulated PTHRP mRNA expression and
secretion and led to a significant reduction in the rate of
proliferation. In contrast, the basal level of PTHRP production
decreased sharply in confluent HCX, and induction by calcium or
exogenous growth factors was reduced or lost. After stable
transfection with HPV-16 and 18 DNAs we observed a sharp decrease of
PTHRP production in high passage poorly differentiated HCX. Finally,
addition of exogenous PTHRP (1-141) inhibited proliferation of both
normal cells and low passage, well-differentiated HPV-16 immortalized
cells. High passage, poorly differentiated cells were refractory to
PTHRP. These results demonstrate that PTHRP production varies greatly
with the degree of cell proliferation and differentiation and suggest
that this peptide acts as an autocrine negative growth regulator for
cervical keratinocytes.
Received 28 August 1995; accepted in final form 26 January 1996.
APS Manuscript Number C529-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 13 March 96