title: HMG-I/Y is a c-Jun/activator protein-1 target gene and is necessary for c-Jun-induced anchorage-independent growth in Rat1a cells.
abstract: The transcription complex activator protein-1 (AP-1) plays a role in a diverse number of cellular processes including proliferation, differentiation, and apoptosis. To identify AP-1-responsive target genes, we used a doxycycline-inducible c-Jun system in Rat1a cells. The HMG-I/Y chromatin binding protein was found to be up-regulated by c-Jun. Following induction of c-Jun expression, Rat1a cells under nonadherent growth conditions have sustained HMG-I/Y mRNA expression and 2-fold higher protein than uninduced cells. HMG-I/Y promoter reporter assays show that HMG-I/Y promoter activity increases in the presence of c-Jun expression, and gel mobility shift assays demonstrate that induced c-Jun binds to an AP-1 consensus site at position -1,091 in the HMG-I/Y promoter. Suppression of HMG-I/Y expression by its antisense sequence significantly reduces the ability of c-Jun-overexpressing Rat1a cells to grow in an anchorage-independent fashion. HMG-I/Y transforms Rat1a cells (although the colonies are smaller than that observed for the cells overexpressing c-Jun). Taken together, these results suggest that HMG-I/Y is a direct transcriptional target of c-Jun necessary for c-Jun-induced anchorage-independent growth in Rat1a cells.
authors.affiliation: Cell and Cancer Biology Branch, National Cancer Institute, Rockville, MD, USA.
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Hommura
authors.forename: Motoo
authors.initials: M
authors.lastname: Katabami
authors.forename: Virna D
authors.initials: VD
authors.lastname: Leaner
authors.forename: Howard
authors.initials: H
authors.lastname: Donninger
authors.forename: Takita F
authors.initials: TF
authors.lastname: Sumter
authors.forename: Linda M S
authors.initials: LM
authors.lastname: Resar
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Birrer
mesh_terms: D000818:Animals; D001665:Binding Sites; D002448:Cell Adhesion; D002460:Cell Line; D049109:Cell Proliferation; D003260:Contact Inhibition; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation; D025741:HMGA1a Protein / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D011401:Promoter Regions, Genetic / Q000235:genetics; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020218:Response Elements / Q000235:genetics; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D025741:HMGA1a Protein