A functional genetic screen identifies retinoic acid signaling as a target of histone deacetylase inhibitors.

A functional genetic screen identifies retinoic acid signaling as a target of histone deacetylase inhibitors. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

A functional genetic screen identifies retinoic acid signaling as a target of histone deacetylase inhibitors. Abstract Text:

Mirjam T Epping,Liming Wang,Jane A Plumb,Michele Lieb,Hinrich Gronemeyer,Robert Brown, Bernards,Mirjam T Epping,Liming Wang,Jane A Plumb,Michele Lieb,Hinrich Gronemeyer,Robert Brown, Bernards,

Understanding the pathways that are targeted by cancer drugs is instrumental for their rational use in a clinical setting. Inhibitors of histone deacetylases (HDACI) selectively inhibit proliferation of malignant cells and are used for the treatment of cancer, but their cancer selectivity is understood poorly. We conducted a functional genetic screen to address the mechanism(s) of action of HDACI. We report here that ectopic expression of two genes that act on retinoic acid (RA) signaling can cause resistance to growth arrest and apoptosis induced by HDACI of different chemical classes: the retinoic acid receptor alpha (RARalpha) and preferentially expressed antigen of melanoma (PRAME), a repressor of RA signaling. Treatment of cells with HDACI induced RA signaling, which was inhibited by RARalpha or PRAME expression. Conversely, RAR-deficient cells and PRAME-knockdown cells show enhanced sensitivity to HDACI in vitro and in mouse xenograft models. Finally, a combination of RA and HDACI acted synergistically to activate RA signaling and inhibit tumor growth. These experiments identify the RA pathway as a rate-limiting target of HDACI and suggest strategies to enhance the therapeutic efficacy of HDACI.

A functional genetic screen identifies retinoic acid signaling as a target of histone deacetylase inhibitors. Publishing Authors By Initials

MT Epping,L Wang,JA Plumb,M Lieb,H Gronemeyer,R Brown,R Bernards,MT Epping,L Wang,JA Plumb,M Lieb,H Gronemeyer,R Brown,R Bernards,

For similar abstracts research abstracts see: abstracts research

PUBMED ID PMID:

MEDLINE DATE:

A functional genetic screen identifies retinoic acid signaling as a target of histone deacetylase inhibitors. Journal Published:

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

Journal: Proceedings of the National Academy of Sciences of

VOLUME: 104

Page Numbers: 17777-82

Journal Abbreviation: Proc. Natl. Acad. Sci. U.S.A.

ISSN: 0027-8424

DAY: 29

MONTH: 10

YEAR: 2007

A functional genetic screen identifies retinoic acid signaling as a target of histone deacetylase inhibitors. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7505876

A functional genetic screen identifies retinoic acid signaling as a target of histone deacetylase inhibitors. Keywords Mesh Terms:

KEYWORDS:

MESH TERMS:

Chemical & Substance for Abstract: A functional genetic screen identifies retinoic acid signaling as a target of histone deacetylase inhibitors. Information

Substance Name:

Registry Number:

Grant and Affiliation Information for A functional genetic screen identifies retinoic acid signaling as a target of histone deacetylase inhibitors.

AFFILIATION: Division of Molecular Carcinogenesis and Center for Biomedical Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.

Country: United States

AGENCY:

GRANT:

ACRONYM:

MEDLINETA: Proc Natl Acad Sci U S A

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

A functional genetic screen identifies retinoic acid signaling as a target of histone deacetylase inhibitors Related Publications

• A RNA interference screen identifies the Protein Phosphatase 2A subunit PR55gamma as a stress-sensitive inhibitor of c-SRC.
• A functional genetic screen identifies retinoic acid signaling as a target of histone deacetylase inhibitors.
• Are short-term or long-term recurrence rates more important in breast cancer screening?
• Cancer: Entangled pathways.
• Dissemination of Bacillus cereus in a paediatric intensive care unit traced to insufficient disinfection of reusable ventilator air-flow sensors.
• E2F-4, a new member of the E2F gene family, has oncogenic activity and associates with p107 in vivo.
• Enabling personalized cancer medicine through analysis of gene-expression patterns.
• PRAME expression and clinical outcome of breast cancer.
• Ras superfamily and interacting proteins database.
• Reaction to American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer.
• Suppression of the p53-Dependent Replicative Senescence Response by Lysophosphatidic Acid Signaling.
• Transforming Growth Factor-{beta} Requires Its Target Plasminogen Activator Inhibitor-1 for Cytostatic Activity.
• rad-dependent response of the chk1-encoded protein kinase at the DNA damage checkpoint.