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Down-regulation of peroxisome proliferator-activated receptor gamma in human cervical carcinoma

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Affiliated Author(s)
차순도조치흠백원기서성일장병철송대규배재훈권건영
Alternative Author(s)
Cha, Soon DoCho, Chi HeumBaek, Won KiSuh, Seong IlJang, Byeong ChurlSong, Dae KyuBae, Jae HoonKwon, Kun Young
Journal Title
Gynecologic Oncology
ISSN
0090-8258
Issued Date
2005
Abstract
Objective. Peroxisome proliferator-activated receptor gamma (PPARg) is a member of the nuclear hormone receptor superfamily.
Treatment of PPARg ligands has been shown to inhibit the growth of various human cancer cells. However, it has not been reported
whether human cervical carcinoma cells express PPARg. In this study, we investigated the expression of PPARg in human normal cervix
and cervical carcinoma tissues, and as well as the effect of PPARg ligands on cervical cancer cells survival.
Methods. Fresh cervical tissues from a study group of 10 study patients diagnosed with cervical carcinoma were analyzed for the
expression of PPARg using real-time RT-PCR and Western blot analysis. Immunohistochemical staining for PPARg was also performed
on the serial sections of 40 cervical carcinomas. In addition, we evaluated the feasibility of PPARg ligands, as a potential therapeutic drug
against cervical cancer cells using MTT assay and FACS analysis.
Results. We found that there were lower expression levels of PPARg mRNA and protein in cervical carcinoma tissues than in normal
cervical tissues. The extent and intensity of immunoreactive PPARg in normal cervix tissues were statistically much greater than those of
carcinoma tissues. In order to study effects of PPAR ligand on cell proliferation, we chose ciglitizone that showed very potent growth
inhibitory effects on the proliferation of two human cervical cancer cell lines (C-33-A and C-4II). C-4II cells express high expression of
PPARg, while C-33A cells express low level of PPARg. Treatment with ciglitizone inhibited the growth of C-4II cells in a dosedependent
manner, while the growth inhibitory effect of ciglitizone was much less in C-33A cells. In order to test whether ciglitizoneinduced
growth suppressive effects on cervical cancer cell lines is PPAR-dependent, we treated cervical cancer cells with ciglitizone and/
or GW9662 (a PPARg antagonist). No significant difference in cell survival was found in cells treated with ciglitizone alone vs. co-treated
with ciglitizone and GW9662. GW9662 alone did not induce any cell growth arrest in the cells that we used (data not shown). Thus, we
concluded that growth suppressive effects by ciglitizone may not be dependent upon status of PPAR expression. To clarify the mechanism
by which ciglitizone inhibits the growth of cervical carcinoma cells, flow cytometry and Western blotting assay were performed. As
results, we demonstrated that a large portion of C-4II cells (but not in C-33A) after ciglitizone treatment were arrest at G1 phase with the
induction of p21Cip1/Waf1 and p27kip1 protein.
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