Expression and action of parathyroid hormone-related peptide in human cervical epithelial cells.
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) types 16 and 18 DNAs. In normal cells, trans-retinoic acid (RA) and 2.0 mM Ca2+ 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 Ca2+ or exogenous growth factors was reduced or lost. After stable transfection with HPV16 and HPV18 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 HPV16 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.
Kremer
R
R
Calcium Research Laboratory, Royal Victoria Hospital, Montreal, Quebec, Canada.
Woodworth
C D
CD
Goltzman
D
D
D002118:Calcium / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed / Q000378:metabolism; D002478:Cells, Cultured; D002584:Cervix Uteri / Q000166:cytology / Q000378:metabolism*; D005260:Female; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism; D027383:Papillomaviridae / Q000502:physiology; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D012016:Reference Values; D014212:Tretinoin / Q000494:pharmacology
D006133:Growth Substances; D009363:Neoplasm Proteins; C470121:PTHLH protein, human; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins; D012333:RNA, Messenger; D014212:Tretinoin; D002118:Calcium