SP1-mediated downregulation of ADAMTS3 gene expression in osteosarcoma models

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dc.contributor.authorAydemir, A. Tuğşen
dc.contributor.authorAlper, Meltem
dc.contributor.authorKoçkar, Feray
dc.date.accessioned13.07.201910:50:10
dc.date.accessioned2019-07-16T09:15:14Z
dc.date.available13.07.201910:50:10
dc.date.available2019-07-16T09:15:14Z
dc.date.issued2018
dc.departmentAksaray Teknik Bilimler Meslek Yüksekokulu
dc.description.abstractADAMTS3 is a member of procollagen N-proteinase subfamily of ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) gene family. It has an important function in the procollagen maturation process. The removal of N-peptidases is required for the accurate processing of fibrillar collagens. Otherwise, several disorders can occur that is related with the collagenous tissues. ADAMTS3 mainly maturates type II collagen molecule which is the main component of the bone and cartilage. There are several expression studies about ADAMTS3 gene however its transcriptional regulation has not been lightened up, yet. Here we first time cloned and functionally analyzed the promoter region of ADAMTS3 gene, approximately 1380 bp upstream of the transcription start site. Transient transfection experiments showed that all truncated promoter constructs are active and 171 bp fragment is sufficient to activate gene expression in both Saos-2 and MG63 cells. In silico analysis showed that ADAMTS3 has a TATA-less promoter and contains several SP1/GC box binding motifs and a CpG island. Therefore we mainly investigated the SP1 dependent regulation of ADAMTS3 promoter. SP1 downregulated ADAMTS3 transcriptional activity. As consistent with the transcriptional activity, mRNA, and protein expression levels were also decreased by SP1. On the other hand, functional binding of the SP1 on multiple regions of ADAMTS3 promoter was confirmed by EMSA studies. As ADAMTS3 is responsible for the collagen maturation and biosynthesis, further we investigated the effect of SP1 on type I II and III collagen gene expressions. We point out that SP1 increased type II and III collagen expression and in contrast decreased type I collagen expression levels in Saos-2 cells. mRNA expression level was decreased for all collagen types in MG63 model. Decrease in the type II collagen expression was also demonstrated at the protein level by SP1. Collectively these results provide first findings for the SP1-related transcriptional regulation of ADAMTS3 and collagen genes in osteosarcoma cell lines.
dc.description.sponsorshipScientific and Technological Research Council of Turkey (TUBITAK) [114Z025]
dc.description.sponsorshipThis work was supported by the Scientific and Technological Research Council of Turkey (TUBITAK) (114Z025).
dc.identifier.doi10.1016/j.gene.2018.03.009
dc.identifier.endpage10en_US
dc.identifier.issn0378-1119
dc.identifier.issn1879-0038
dc.identifier.pmid29518549
dc.identifier.scopusqualityQ2
dc.identifier.startpage1en_US
dc.identifier.urihttps://doi.org/10.1016/j.gene.2018.03.009
dc.identifier.urihttps://hdl.handle.net/20.500.12451/4329
dc.identifier.volume659en_US
dc.identifier.wosWOS:000433015400001
dc.identifier.wosqualityN/A
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherElsevier Science Bv
dc.relation.ispartofGENE
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/embargoedAccess
dc.subjectADAMTS3
dc.subjectSP1
dc.subjectOsteosarcoma
dc.subjectTranscriptional Regulation
dc.subjectSaos-2
dc.subjectMG-63
dc.titleSP1-mediated downregulation of ADAMTS3 gene expression in osteosarcoma models
dc.typeArticle

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