Journal article
Epigenetic-mediated upregulation of progesterone receptor B gene in endometrial cancer cell lines
Gynecologic oncology, Vol.99(1), pp.135-141
2005
DOI: 10.1016/j.ygyno.2005.05.035
PMID: 16024066
Abstract
To determine if epigenetic interference can restore progesterone receptor-B (PR-B) expression in PR-B negative endometrial adenocarcinoma cell lines, and to characterize the kinetics of PR-B induction mediated by DNA methyltransferase and histone deacetylase inhibitors.
The PR-B negative endometrioid cancer cell lines KLE and HEC-1B were used as study models. PR-B mRNA and protein expression levels were measured using real-time PCR and Western blot analysis, respectively. DNA methylation levels of the PR-B promoter were determined by methylation-specific PCR. Dose–response correlations and the duration of response to aza-deoxycytidine (ADC) and trichostatin A (TSA) were characterized. Cell responses to prolonged and repeated drug treatment were also examined.
Relatively low concentrations of ADC and TSA over a 24-h period induced PR-B expression. Furthermore, ADC and TSA acted synergistically to reactivate PR-B expression. Depending on the cell line used, PR-B mRNA was induced 10–110 fold. This elevated PR-B expression continued for 48 h after drug withdrawal. Sustained upregulation of PR-B mRNA and protein was observed during prolonged and repeated drug treatment.
The epigenetically silenced PR-B gene remains sensitive to changes in DNA demethylation and histone acetylation in uterine adenocarcinoma cell lines. Treatment with ADC and/or TSA results in a robust and sustainable PR-B upregulation. These small molecule epigenetic modifying agents may be used to sensitize poorly differentiated, PR-B negative endometrial cancers to progestational therapy.
Details
- Title: Subtitle
- Epigenetic-mediated upregulation of progesterone receptor B gene in endometrial cancer cell lines
- Creators
- Yuning Xiong - Mayo ClinicSean C. Dowdy - Mayo ClinicJesus Gonzalez Bosquet - Mayo ClinicYing Zhao - Mayo ClinicNorman L. Eberhardt - Department of Medicine, Division of Endocrinology, Mayo Clinic and Foundation, Rochester, MN 55905, USAKarl C. Podratz - Mayo ClinicShi-Wen Jiang - Mayo Clinic
- Resource Type
- Journal article
- Publication Details
- Gynecologic oncology, Vol.99(1), pp.135-141
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.ygyno.2005.05.035
- PMID
- 16024066
- ISSN
- 0090-8258
- eISSN
- 1095-6859
- Language
- English
- Date published
- 2005
- Academic Unit
- Obstetrics and Gynecology
- Record Identifier
- 9984315562702771
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