Oncogene. 2008 Jun 5;27(25):3605-14. Epub 2008 Jan 28.

Runx2-mediated activation of the Bax gene increases osteosarcoma cell sensitivity to apoptosis.

Eliseev RA, Dong YF, Sampson E, Zuscik MJ, Schwarz EM, O'Keefe RJ, Rosier RN, Drissi MH.

Source

Department of Orthopaedics, Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY, USA.

Abstract

The Runx family of transcription factors regulate cell growth and differentiation, and control the expression of target genes involved in cell fate decisions. We examined the role of the bone-related member of this family, Runx2, in regulating apoptosis via modulation of the Bcl2 family of genes in the osteosarcoma cell line Saos2. Our data demonstrate that Runx2 directly binds to two Runx-specific regulatory elements on the human bax promoter thereby inducing Bax expression. Furthermore, bone morphogenetic protein-induced or vector-mediated expression of Runx2 resulted in upregulation of Bax expression, and subsequent increased sensitivity of Saos2 cells to apoptosis. Finally, the observed upregulation of Bax expression and increased apoptosis were Runx2 dependent as Runx2 loss of function abrogated these effects. Our study provides the first evidence for Bax as a direct target of Runx2, suggesting that Runx2 may act as a proapoptotic factor in osteosarcoma cells.

PMID:: 18223689; [PubMed - indexed for MEDLINE]

LinkOut - more resources

Full Text Sources

Other Literature Sources

COS Scholar Universe

Medical

Supplemental Content

Related citations

Smad7 mediates inhibition of Saos2 osteosarcoma cell differentiation by NFkappaB. [Exp Cell Res. 2006]
Smad7 mediates inhibition of Saos2 osteosarcoma cell differentiation by NFkappaB.
Eliseev RA, Schwarz EM, Zuscik MJ, O'Keefe RJ, Drissi H, Rosier RN. Exp Cell Res. 2006 Jan 1; 312(1):40-50. Epub 2005 Nov 2.
Regulation of TGFbeta1-mediated growth inhibition and apoptosis by RUNX2 isoforms in endothelial cells. [Oncogene. 2004]
Regulation of TGFbeta1-mediated growth inhibition and apoptosis by RUNX2 isoforms in endothelial cells.
Sun L, Vitolo MI, Qiao M, Anglin IE, Passaniti A. Oncogene. 2004 Jun 10; 23(27):4722-34.
RUNX2 regulates the effects of TNFalpha on proliferation and apoptosis in SaOs-2 cells. [Bone. 2010]
RUNX2 regulates the effects of TNFalpha on proliferation and apoptosis in SaOs-2 cells.
Olfa G, Christophe C, Philippe L, Romain S, Khaled H, Pierre H, Odile B, Jean-Christophe D. Bone. 2010 Apr; 46(4):901-10. Epub 2010 Jan 4.
Review Regulatory roles of Runx2 in metastatic tumor and cancer cell interactions with bone. [Cancer Metastasis Rev. 2006]
Review Regulatory roles of Runx2 in metastatic tumor and cancer cell interactions with bone.
Pratap J, Lian JB, Javed A, Barnes GL, van Wijnen AJ, Stein JL, Stein GS. Cancer Metastasis Rev. 2006 Dec; 25(4):589-600.
Review Runx2: of bone and stretch. [Int J Biochem Cell Biol. 2008]
Review Runx2: of bone and stretch.
Ziros PG, Basdra EK, Papavassiliou AG. Int J Biochem Cell Biol. 2008; 40(9):1659-63. Epub 2007 Jun 26.

See reviews... See all...

Cited by 9 PubMed Central articles

Wip1 promotes RUNX2-dependent apoptosis in p53-negative tumors and protects normal tissues during treatment with anticancer agents. [Proc Natl Acad Sci U S A. 2012]
Wip1 promotes RUNX2-dependent apoptosis in p53-negative tumors and protects normal tissues during treatment with anticancer agents.
Goloudina AR, Tanoue K, Hammann A, Fourmaux E, Le Guezennec X, Bulavin DV, Mazur SJ, Appella E, Garrido C, Demidov ON. Proc Natl Acad Sci U S A. 2012 Jan 10; 109(2):E68-75. Epub 2011 Nov 7.
The Role of RUNX2 in Osteosarcoma Oncogenesis. [Sarcoma. 2011]
The Role of RUNX2 in Osteosarcoma Oncogenesis.
Martin JW, Zielenska M, Stein GS, van Wijnen AJ, Squire JA. Sarcoma. 2011; 2011:282745. Epub 2010 Dec 9.
Impaired cell cycle regulation of the osteoblast-related heterodimeric transcription factor Runx2-Cbfbeta in osteosarcoma cells. [J Cell Physiol. 2009]
Impaired cell cycle regulation of the osteoblast-related heterodimeric transcription factor Runx2-Cbfbeta in osteosarcoma cells.
San Martin IA, Varela N, Gaete M, Villegas K, Osorio M, Tapia JC, Antonelli M, Mancilla EE, Pereira BP, Nathan SS, et al. J Cell Physiol. 2009 Dec; 221(3):560-71.

See all...

Related information

Related Citations
Calculated set of PubMed citations closely related to the selected article(s) retrieved using a word weight algorithm. Related articles are displayed in ranked order from most to least relevant, with the “linked from” citation displayed first.
Gene
Gene records that cite the current articles. Citations in Gene are added manually by NCBI or imported from outside public resources.
Gene (GeneRIF)
Gene records that have the current articles as Reference into Function citations (GeneRIFs). NLM staff reviewing the literature while indexing MEDLINE add GeneRIFs manually.
HomoloGene
HomoloGene clusters of homologous genes and sequences that cite the current articles. These are references on the Gene and sequence records in the HomoloGene entry.
Nucleotide (RefSeq)
NCBI nucleotide Reference Sequences (RefSeqs) that are cited in the current articles, included in the corresponding Gene Reference into Function, or that include the PubMed articles as references.
Nucleotide (Weighted)
Nucleotide records associated with the current articles through the Gene database. These are the related sequences on the Gene record that are added manually by NCBI.
Protein (RefSeq)
NCBI protein Reference Sequences (RefSeqs) that are cited in the current articles, included in the corresponding Gene Reference into Function, or that include the PubMed articles as references.
Protein (Weighted)
Protein records associated with the current articles through related Gene database records. These are the related sequences on the Gene record that are added manually by NCBI.
Taxonomy via GenBank
Taxonomy records associated with the current articles through taxonomic information on related molecular database records (Nucleotide, Protein, Gene, SNP, Structure).
UniGene
UniGene clusters of expressed sequences that are associated with the current articles through references on the clustered sequence records and related Gene records.
GEO Profiles
Gene Expression Omnibus (GEO) Profiles of molecular abundance data. The current articles are references on the Gene record associated with the GEO profile.
Cited in PMC
Full-text articles in the PubMed Central Database that cite the current articles.

Recent activity

Clear Turn Off Turn On

Runx2-mediated activation of the Bax gene increases osteosarcoma cell sensitivit...
Runx2-mediated activation of the Bax gene increases osteosarcoma cell sensitivity to apoptosis.
Oncogene. 2008 Jun 5 ;27(25):3605-14. Epub 2008 Jan 28 .

PubMed
Measles, mumps and rubella -- the urologist's perspective.
Measles, mumps and rubella -- the urologist's perspective.
Int J Clin Pract. 2006 Mar ;60(3):335-9.

PubMed
Myasthenia gravis: emerging new therapy options.
Myasthenia gravis: emerging new therapy options.
Curr Opin Pharmacol. 2005 Jun ;5(3):303-7.

PubMed
Applying phylogenetic analysis to viral livestock diseases: moving beyond molecu...
Applying phylogenetic analysis to viral livestock diseases: moving beyond molecular typing.
Vet J. 2010 May ;184(2):130-7. Epub 2009 Mar 28 .

PubMed
A randomized controlled trial of exercise and manipulative therapy for cervicoge...
A randomized controlled trial of exercise and manipulative therapy for cervicogenic headache.
Spine (Phila Pa 1976). 2002 Sep 1 ;27(17):1835-43; discussion 1843.

PubMed

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

PubMed

Display Settings:

Send to:

Runx2-mediated activation of the Bax gene increases osteosarcoma cell sensitivity to apoptosis.

Source

Abstract

Publication Types, MeSH Terms, Substances, Grant Support

Publication Types

MeSH Terms

Substances

Grant Support

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Supplemental Content

Related citations

Cited by 9 PubMed Central articles

Related information

Recent activity

Simple NCBI Directory

Getting Started

Resources

Popular

Featured

NCBI Information