Document Detail

The interplay between histone deacetylases and c-Myc in the transcriptional suppression of HPP1 in colon cancer.
MedLine Citation:
PMID:  24919179     Owner:  NLM     Status:  Publisher    
HPP1 (hyperplastic polyposis protein 1), a tumor suppressor gene, is downregulated by promoter hypermethylation in a number of tumor types including colon cancer. c-Myc is also known to play a role in the suppression of HPP1 expression via binding to a promoter region cognate E-box site. The contribution of histone deacetylation as an additional epigenetic mechanism and its potential interplay with c-Myc in the transcriptional regulation of HPP1 are unknown. We have shown that the treatment of the HPP1-non-expressing colon cancer cell lines, HCT116 and DLD-1 with HDAC inhibitors results in re-expression of HPP1. RNAi-mediated knockdown of c-Myc as well as of HDAC2 and HDAC3 in HCT116 and of HDAC1 and HDAC3 in DLD-1 also resulted in significant re-expression of HPP1. Co-immunoprecipitation (IP), chromatin IP (ChIP), and sequential ChIP experiments demonstrated binding of c-Myc to the HPP1 promoter with recruitment of and direct interaction with HDAC3. In summary, we have demonstrated that c-Myc contributes to the epigenetic regulation of HPP1 via the dominant recruitment of HDAC3. Our findings may lead to a greater biologic understanding for the application of targeted use of HDAC inhibitors for anti-cancer therapy.
Jian Wang; Abul Elahi; Abidemi Ajidahun; Whalen Clark; Jonathan Hernandez; Alex Achille; Ji-Hui Hao; Edward Seto; David Shibata
Related Documents :
24024169 - Sex hormones modulate circulating antioxidant enzymes: impact of estrogen therapy.
1691249 - Molecular mechanisms underlying erythropoiesis: cycling activity of adult bfu-e relates...
24964229 - Transcriptional regulation by infliximab therapy in kawasaki disease patients with immu...
24002729 - A potential new therapeutic approach for friedreich ataxia: induction of frataxin expre...
8329139 - Stress-associated modulation of proto-oncogene expression in human peripheral blood leu...
1376749 - Independent regulation of c-myc, b-myb, and c-myb gene expression by inducers and inhib...
22366449 - Inhibition of mrna maturation in trypanosomes causes the formation of novel foci at the...
20876509 - Neonatal stroke in mice causes long-term changes in neuronal notch-2 expression that ma...
22371739 - Cyclic tensile stretch modulates osteogenic differentiation of adipose-derived stem cel...
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-6-11
Journal Detail:
Title:  Cancer biology & therapy     Volume:  15     ISSN:  1555-8576     ISO Abbreviation:  Cancer Biol. Ther.     Publication Date:  2014 Jun 
Date Detail:
Created Date:  2014-6-11     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101137842     Medline TA:  Cancer Biol Ther     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Long-lasting, kin-directed female interactions in a spatially structured wild boar social network.
Next Document:  Intra-Myocardial Injection of Both Growth Factors and Heart Derived Sca-1+/CD31- Cells Attenuates Po...