Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1997-3-10
pubmed:abstractText
Retinoids are important regulators of human papillomavirus (HPV)-immortalized cervical epithelial cell differentiation and have been successfully used in the treatment of HPV-involved cervical cancer. In the present study, we examine the effects of a series of natural and synthetic retinoids on differentiation and proliferation of HPV-16-positive lines, ECE16-1 and CaSki. Retinoic acid receptor alpha (RAR alpha), RAR gamma, and retinoid X receptor alpha (RXR alpha) are the major retinoid receptor subtypes expressed when ECE16-1 cells are grown in retinoid-free medium. Our results indicate that ligands that interact with RARs only or both RARs and RXRs, including all-trans-retinoic acid (all-trans-RA), 9-cis-retinoic acid (9-cis-RA), 13-cis-retinoic acid (13-cis-RA), and several synthetic retinoids, suppress ECE16-1 cell proliferation, regulate expression of the retinoid-responsive differentiation marker cytokeratin K5, and increase RAR beta mRNA levels. In contrast, ligands that specifically interact with RXRs do not suppress proliferation and are less efficient regulators of gene expression. CaSki cells express greatly reduced RAR and RXR levels compared to ECE16-1 cells. However, both RAR- and RXR-specific ligands increase CaSki number by > or = 20%. In addition, RXR-specific ligands suppress cytokeratin K5 mRNA levels slightly, compared to RAR-specific ligands that strongly suppress K5 mRNA levels. We also compare the effects of these agents on the proliferation of other cervical cell lines, including ECE16-D2, ME180, and SiHa cells. ECE16-D2 and ME180 cells are growth suppressed by RAR-specific, but not RXR-specific, retinoids. SiHa cells are not responsive to either class of retinoid. Our results indicate that: (a) the response of different human cervical cell lines varies following treatment with receptor type-specific retinoids; and (b) the relationship between retinoid regulation of proliferation and differentiation can be uncoupled.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1044-9523
pubmed:author
pubmed:issnType
Print
pubmed:volume
7
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
521-30
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Differential regulation of human ectocervical epithelial cell line proliferation and differentiation by retinoid X receptor- and retinoic acid receptor-specific retinoids.
pubmed:affiliation
Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, OH 44106-4970, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't