Titre du document / Document title

Aberrant methylation and silencing of the calponin gene in human sarcoma cells

Auteur(s) / Author(s)

YAMAMURA Hisako ⁽¹⁾ ; YOSHIKAWA Hideki ⁽²⁾ ; TAKAHASHI Katsuhito ⁽¹⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Department of Molecular Medicine and Pathophysiology, Osaka Medical Center for Cancer and Cardiovascular Diseases, The Graduate School of Pharmaceutical Science, Osaka University, SORST, Japan Science and Technology Corporation (JST), Osaka 537-8511, JAPON
⁽²⁾ Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, Osaka 569-0801, JAPON

Résumé / Abstract

Background: We have recently developed a new strategy for the treatment of sarcomas by using human calponin promoter to drive replication and oncolysis of herpes simplex virus (HSV-1). In order to apply this therapy to a broad spectrum of sarcoma cells, it is essential to elucidate silencing mechanisms of the calponin promoter in a subset of sarcoma cells. Materials and Methods: In this study, we investigated the mechanisms of calponin inactivation in human sarcoma tissues and cell lines through the analysis of CpG methylation of promoter region by bisulfite modification, because the 5'-flanking region of the human calponin gene was originally identified as a DNA fragment bound to the conserved methyl-CpG binding domain (MBD) of MeCP2. Furthermore, we examined the correlation between DNA methylation and expression of the calponin gene by treatment with the demethylating agent 5-Aza-CdR, and in vitro 5'CpG methylation in a luciferase reporter gene construct. Results: Here, we have provided evidence that DNA hypermethylation of the specific 5'CpG sites in exon 1 is a mechanism accompanying decreased calponin expression in both human sarcoma tissues and cell lines. Conclusion: These results suggest that DNA methylation may be an important mechanism regulating calponin transcription in human sarcoma cells, and thus could potentially affect the efficacies of treatment of this malignancy utilizing the human calponin promoter.

Revue / Journal Title

Anticancer research   ISSN 0250-7005 

Source / Source

2003, vol. 23, n^o1A, pp. 107-114 [8 page(s) (article)] (26 ref.)

Langue / Language

Anglais

Editeur / Publisher

International Institute of Anticancer Research, Attiki, GRECE  (1980) (Revue)

Mots-clés anglais / English Keywords

Genetics ; Malignant tumor ; Calponin ; Smooth muscle ; Human ; Gene silencing ; Methylation ; Leiomyosarcoma ;

Mots-clés français / French Keywords

Génétique ; Tumeur maligne ; Calponine ; Muscle lisse ; Homme ; Silence expression génique ; Méthylation ; Léiomyosarcome ;

Mots-clés espagnols / Spanish Keywords

Genética ; Tumor maligno ; Músculo liso ; Hombre ; Silencio expresión genética ; Metilación ; Leiomiosarcoma ;

Mots-clés d'auteur / Author Keywords

Calponin gene ; sarcoma cells ; human ; methylation ;

Localisation / Location

INIST-CNRS, Cote INIST : 19426, 35400011075596.0160