AP-2 regulates the transcription of estrogen receptor (ER)-beta by acting through a methylation hotspot of the 0N promoter in prostate cancer cells.

AP-2 regulates the transcription of estrogen receptor (ER)-beta by acting through a methylation hotspot of the 0N promoter in prostate cancer cells. Research Abstract Details 

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AP-2 regulates the transcription of estrogen receptor (ER)-beta by acting through a methylation hotspot of the 0N promoter in prostate cancer cells. Abstract Text:

X Zhang,Y-K Leung,S-M Ho,X Zhang,Y-K Leung,S-M Ho,

We reported previously that the loss of expression of estrogen receptor (ER)-beta during the development of prostate cancer (PCa) is associated with methylation of a CpG island located in the 5'-flanking sequence of the 0N promoter. Three methylation hotspots, referred to as centers 1, 2 and 3, were identified in the CpG island. In this study, we demonstrated that a 581-bp region with these three centers within it is sufficient for the promoter activity in PCa cells. Deletion analyses indicated that center 1 (16 bp), with a putative activator protein-2 (AP-2) binding site, is essential for gene transactivation. Chromatin immunoprecipitation assays showed that AP-2alpha occupies a short sequence containing center 1. Forced expression of AP-2alpha or -2gamma, but not -2beta, increased activity of the ERbeta 0N promoter and the accumulation of mRNA. Conversely, siRNA-mediated AP-2alpha and -2gamma knockdown reduced levels of ERbeta transcript and promoter activity. Quantitative reverse transcription-PCR showed that AP-2alpha and -2gamma are the predominant transcripts expressed in PCa cells, and levels of ERbeta transcript correlate with levels of these AP-2 transcripts among different PCa cell lines. These results provide the first evidence that ERbeta is an AP-2-regulated gene. They also support the hypothesis that certain cis-acting elements are methylation hotspots susceptible to epigenetic modifications during cancer progression.

AP-2 regulates the transcription of estrogen receptor (ER)-beta by acting through a methylation hotspot of the 0N promoter in prostate cancer cells. Publishing Authors By Initials

X Zhang,YK Leung,SM Ho,X Zhang,YK Leung,SM Ho,

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AP-2 regulates the transcription of estrogen receptor (ER)-beta by acting through a methylation hotspot of the 0N promoter in prostate cancer cells. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Oncogene

VOLUME: 26

Page Numbers: 7346-54

Journal Abbreviation: Oncogene

ISSN: 1476-5594

DAY: 21

MONTH: 05

YEAR: 2007

AP-2 regulates the transcription of estrogen receptor (ER)-beta by acting through a methylation hotspot of the 0N promoter in prostate cancer cells. Information

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LANGUAGE: eng

NlmUniqueID: 8711562

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Grant and Affiliation Information for AP-2 regulates the transcription of estrogen receptor (ER)-beta by acting through a methylation hotspot of the 0N promoter in prostate cancer cells.

AFFILIATION: Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0056, USA.

Country: England

AGENCY: United States NIDDK

GRANT: DK061084

ACRONYM: DK

MEDLINETA: Oncogene

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