Activated signal transducers and activators of transcription 3 signaling induces CD46 expression and protects human cancer cells from complement-dependent cytotoxicity.

Activated signal transducers and activators of transcription 3 signaling induces CD46 expression and protects human cancer cells from complement-dependent cytotoxicity. Research Abstract Details 

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Activated signal transducers and activators of transcription 3 signaling induces CD46 expression and protects human cancer cells from complement-dependent cytotoxicity. Abstract Text:

Ralf Buettner,Mei Huang,Tanya Gritsko,Jim Karras,Steve Enkemann,Tania Mesa,Sangkil Nam,Hua Yu,Richard Jove,

CD46 is one of the complement-regulatory proteins expressed on the surface of normal and tumor cells for protection against complement-dependent cytotoxicity. Cancer cells need to access the blood circulation for continued growth and metastasis, thus exposing themselves to destruction by complement system components. Previous studies have established that the signal transducers and activators of transcription 3 (STAT3) transcription factor is persistently activated in a wide variety of human cancer cells and primary tumor tissues compared with their normal counterparts. Using microarray gene expression profiling, we identified the CD46 gene as a target for activated STAT3 signaling in human breast and prostate cancer cells. The CD46 promoter contains two binding sites for activated STAT3 and mutations introduced into the major site abolished STAT3 binding. Chromatin immunoprecipitation confirms binding of STAT3 to the CD46 promoter. CD46 promoter activity is induced by activation of STAT3 and blocked by a dominant-negative form of STAT3 in luciferase reporter assays. CD46 mRNA expression is induced by interleukin-6 and by transient transfection of normal human epithelial cells with a persistently active mutant construct of STAT3, STAT3C. Furthermore, we show that inhibition of STAT3-mediated CD46 cell surface expression sensitizes DU145 prostate cancer cells to cytotoxicity in an in vitro complement lysis assay using rabbit anti-DU145 antiserum and rabbit complement. These results show that activated STAT3 signaling induces the CD46 promoter and protects human cancer cells from complement-dependent cytotoxicity, suggesting a potential mechanism whereby oncogenic signaling contributes to tumor cell evasion of antibody-mediated immunity.

Activated signal transducers and activators of transcription 3 signaling induces CD46 expression and protects human cancer cells from complement-dependent cytotoxicity. Publishing Authors By Initials

R Buettner,M Huang,T Gritsko,J Karras,S Enkemann,T Mesa,S Nam,H Yu,R Jove,

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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Activated signal transducers and activators of transcription 3 signaling induces CD46 expression and protects human cancer cells from complement-dependent cytotoxicity. Journal Published:

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

Journal: Molecular cancer research : MCR

VOLUME: 5

Page Numbers: 823-32

Journal Abbreviation: Mol. Cancer Res.

ISSN: 1541-7786

DAY: 3

MONTH: Aug

YEAR: 2007

Activated signal transducers and activators of transcription 3 signaling induces CD46 expression and protects human cancer cells from complement-dependent cytotoxicity. Information

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LANGUAGE: eng

NlmUniqueID: 101150042

Activated signal transducers and activators of transcription 3 signaling induces CD46 expression and protects human cancer cells from complement-dependent cytotoxicity. Keywords Mesh Terms:

KEYWORDS: Transfection

MESH TERMS: metabolism

Chemical & Substance for Abstract: Activated signal transducers and activators of transcription 3 signaling induces CD46 expression and protects human cancer cells from complement-dependent cytotoxicity. Information

Substance Name: Luciferases

Registry Number: EC 1.13.12.-

Grant and Affiliation Information for Activated signal transducers and activators of transcription 3 signaling induces CD46 expression and protects human cancer cells from complement-dependent cytotoxicity.

AFFILIATION: Molecular Medicine, Beckman Research Institute, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA. rbuettner@coh.org

Country: United States

AGENCY: United States NCI

GRANT: CA82533

ACRONYM: CA

MEDLINETA: Mol Cancer Res

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