Selenium inhibition of survivin expression by preventing Sp1 binding to its promoter.

Selenium inhibition of survivin expression by preventing Sp1 binding to its promoter. Research Abstract Details 

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Selenium inhibition of survivin expression by preventing Sp1 binding to its promoter. Abstract Text:

Jae Yeon Chun,Yan Hu,Elaine Pinder,Jianguo Wu,Fengzhi Li,Allen C Gao,

Survivin, an antiapoptotic protein highly expressed in cancer, regulates multiple cellular network associated with cancer cell viability and drug resistance. Inhibition of survivin expression has been pursued as a valid cancer therapeutic target. In this study, we showed that selenium, an effective chemopreventive agent for many types of cancers, down-regulated survivin expression. Selenium inhibited survivin expression in both mRNA and protein levels in a dose- and time-dependent manner. Using a series of survivin promoter-luciferase constructs, a 37-bp DNA element in the survivin core promoter region that mediates the ability of selenium to inhibit survivin transcription was identified. Gel mobility shift assays and chromatin immunoprecipitation analyses revealed that selenium prevents the binding of Sp1 or Sp1-like proteins to the 37-bp cis-acting DNA element in the survivin promoter. Furthermore, inhibition of survivin expression by small interfering RNA enhanced selenium's inhibitory effects on cell growth, whereas overexpression of survivin in LNCaP human prostate cancer cells desensitized cancer cells to selenium effect, suggesting that the expression of survivin plays an important role in determining the response of cancer cells to selenium. Taken together, these results suggest that selenium down-regulated survivin expression by preventing the binding of Sp1 or Sp1-like proteins to the promoter of survivin, which contributes at least in part to the inhibitory effect of selenium on survivin gene transcription. In addition, down-regulation of survivin expression may account for one of the molecular mechanisms of the anticancer effects of selenium.

Selenium inhibition of survivin expression by preventing Sp1 binding to its promoter. Publishing Authors By Initials

JY Chun,Y Hu,E Pinder,J Wu,F Li,AC Gao,

For similar investigative techniques: genetic techniques: gene transfer techniques: transfection research abstracts see: investigative techniques: genetic techniques: gene transfer techniques: transfection research

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Selenium inhibition of survivin expression by preventing Sp1 binding to its promoter. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Molecular cancer therapeutics

VOLUME: 6

Page Numbers: 2572-80

Journal Abbreviation: Mol. Cancer Ther.

ISSN: 1535-7163

DAY: 27

MONTH: Sep

YEAR: 2007

Selenium inhibition of survivin expression by preventing Sp1 binding to its promoter. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 101132535

Selenium inhibition of survivin expression by preventing Sp1 binding to its promoter. Keywords Mesh Terms:

KEYWORDS: Transfection

MESH TERMS: drug effects

Chemical & Substance for Abstract: Selenium inhibition of survivin expression by preventing Sp1 binding to its promoter. Information

Substance Name: Luciferases

Registry Number: EC 1.13.12.-

Grant and Affiliation Information for Selenium inhibition of survivin expression by preventing Sp1 binding to its promoter.

AFFILIATION: Department of Medicine, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA.

Country: United States

AGENCY: United States NCI

GRANT: CA109481

ACRONYM: CA

MEDLINETA: Mol Cancer Ther

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