Butyrate activates the WAF1/Cip1 gene promoter through Sp1 sites in a p53-negative human colon cancer cell line.
J Biol Chem
; 272(35): 22199-206, 1997 Aug 29.
Article
in En
| MEDLINE
| ID: mdl-9268365
ABSTRACT
Butyrate is a well known colonic luminal short chain fatty acid, which arrests cell growth and induces differentiation in various cell types. We examined the effect of butyrate on the expression of WAF1/Cip1, a potent inhibitor of cyclin-dependent kinases, and its relation to growth arrest in a p53-mutated human colon cancer cell line WiDr. Five millimolar butyrate completely inhibited the growth of WiDr and caused G1-phase arrest. WAF1/Cip1 mRNA was rapidly induced within 3 h by treatment with 5.0 mM butyrate, and drastic WAF1/Cip1 protein induction was detected. Using several mutant WAF1/Cip1 promoter fragments, we found that the butyrate-responsive elements are two Sp1 sites at -82 and -69 relative to the transcription start site. We also found that a TATA element at -46 and two overlapping consensus Sp1 sites at -60 and -55 are essential for the basal promoter activity of WAF1/Cip1. These findings suggest that butyrate arrests the growth of WiDr by activating the WAF1/Cip1 promoter through specific Sp1 sites in a p53-independent fashion.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Butyrates
/
Gene Expression Regulation
/
Tumor Suppressor Protein p53
/
Sp1 Transcription Factor
/
Promoter Regions, Genetic
/
Cyclins
/
Colonic Neoplasms
Limits:
Humans
Language:
En
Journal:
J Biol Chem
Year:
1997
Document type:
Article
Affiliation country: