Advanced Search

Show simple item record

dc.contributor.authorAlper, Meltem
dc.contributor.authorAydemir, Ayşe Tugşen
dc.contributor.authorKöçkar, Feray
dc.date.accessioned2019-06-24T07:01:52Z
dc.date.available2019-06-24T07:01:52Z
dc.date.issued2018en_US
dc.identifier.urihttps://doi.org/10.1016/j.gene.2018.03.009
dc.identifier.urihttps://hdl.handle.net/20.500.12462/5539
dc.descriptionAydemir, Ayşe Tuğşen (Balikesir Author)en_US
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.en_US
dc.language.isoengen_US
dc.publisherElsevier Scienceen_US
dc.relation.isversionof10.1016/j.gene.2018.03.009en_US
dc.rightsinfo:eu-repo/semantics/embargoedAccessen_US
dc.subjectADAMTS3en_US
dc.subjectSP1en_US
dc.subjectOsteosarcomaen_US
dc.subjectTranscriptional Regulationen_US
dc.subjectSaos-2en_US
dc.subjectMG-63en_US
dc.titleSP1-mediated downregulation of ADAMTS3 gene expression in osteosarcoma modelsen_US
dc.typearticleen_US
dc.relation.journalGeneen_US
dc.contributor.departmentFen Edebiyat Fakültesien_US
dc.identifier.volume659en_US
dc.identifier.startpage1en_US
dc.identifier.endpage10en_US
dc.relation.tubitakinfo:eu-repo/grantAgreement/TUBITAK/114Z025en_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record