Induction of apoptosis of human primary osteoclasts treated with a transcription factor decoy mimicking a promoter region of estrogen receptor alpha.
In this paper we investigated how the increase of human estrogen receptor alfa (ERalpha) gene expression may affect breast, osteoblast and osteoclast cells. Increase of ERalpha expression was obtained by interfering with the activity of a negative transcription factor and by removing it with a short and powerful decoy oligonucleotide (RA4-3') mimicking a region of distal promoter C of ERalpha gene. We provide evidence that this decoy was able to induce apoptosis in osteoclasts, but not in osteoblasts and in breast cancer cells, in an estrogen dependent manner. This effect was associated with increase of the levels of Caspase 3 and Fas receptor. Since ERalpha is important in the transcription of different genes and is involved in several pathological processes, including neoplastic and osteopenic diseases, our findings may be of relevance for a possible new therapeutical approach of such diseases.
Piva
R
R
Department of Biochemistry and Molecular Biology, Ferrara University, Via Fossato di Mortara n.74, 44100 Ferrara, Italy.
Penolazzi
L
L
Lambertini
E
E
Giordano
S
S
Gambari
R
R
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001483:Base Sequence; D001943:Breast Neoplasms / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D020287:In Situ Nick-End Labeling; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D010006:Osteoblasts / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000494:pharmacology*; D014162:Transfection
D047628:Estrogen Receptor alpha; D009838:Oligodeoxyribonucleotides; D014157:Transcription Factors; D004958:Estradiol