title: Sp1 is a transcription repressor to stanniocalcin-1 expression in TSA-treated human colon cancer cells, HT29.
abstract: Our previous study demonstrated that, stanniocalcin-1 (STC1) was a target of histone deacetylase (HDAC) inhibitors and was involved in trichostatin A (TSA) induced apoptosis in the human colon cancer cells, HT29. In this study, we reported that the transcriptional factor, specificity protein 1 (Sp1) in association with retinoblastoma (Rb) repressed STC1 gene transcription in TSA-treated HT29 cells. Our data demonstrated that, a co-treatment of the cells with TSA and Sp1 inhibitor, mithramycin A (MTM) led to a marked synergistic induction of STC1 transcript levels, STC1 promoter (1 kb)-driven luciferase activity and an increase of apoptotic cell population. The knockdown of Sp1 gene expression in TSA treated cells, revealed the repressor role of Sp1 in STC1 transcription. Using a protein phosphatase inhibitor okadaic acid (OKA), an increase of Sp1 hyperphosphorylation and so a reduction of its transcriptional activity, led to a significant induction of STC1 gene expression. Chromatin immunoprecipitation (ChIP) assay revealed that Sp1 binding on STC1 proximal promoter in TSA treated cells. The binding of Sp1 to STC1 promoter was abolished by the co-treatment of MTM or OKA in TSA-treated cells. Re-ChIP assay illustrated that Sp1-mediated inhibition of STC1 transcription was associated with the recruitment of another repressor molecule, Rb. Collectively our findings identify STC1 is a downstream target of Sp1.
authors.affiliation: Department of Biology, Hong Kong Baptist University, Kowloon Tong, Hong Kong.
authors.forename: Alice Y S
authors.initials: AY
authors.lastname: Law
authors.forename: B H Y
authors.initials: BH
authors.lastname: Yeung
authors.forename: L Y
authors.initials: LY
authors.lastname: Ching
authors.forename: Chris K C
authors.initials: CK
authors.lastname: Wong
mesh_terms: D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects* / Q000235:genetics; D006023:Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D019319:Okadaic Acid / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects / Q000235:genetics; D008926:Plicamycin / Q000031:analogs & derivatives / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics
chemical_list: D004791:Enzyme Inhibitors; D006023:Glycoproteins; D006877:Hydroxamic Acids; D011500:Protein Synthesis Inhibitors; D012097:Repressor Proteins; D016160:Retinoblastoma Protein; D016329:Sp1 Transcription Factor; D019319:Okadaic Acid; C012589:trichostatin A; C051795:teleocalcin; C066851:mithramycin A; D008926:Plicamycin