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Loss of cyclin g1 expression in human uterine leiomyoma cells induces apoptosis
- Source :
- Reproductive sciences (Thousand Oaks, Calif.). 15(4)
- Publication Year :
- 2008
-
Abstract
- Observations from the authors' laboratory suggest a physiological role for increased cyclin G1 protein levels in human uterine leiomyoma. The hypothesis of the present study is that the strategic modulation of cyclin G1 by antisense technology will inhibit the survival of in vitro-grown uterine leiomyoma cells. Cultured uterine leiomyoma cells were transfected with cyclin G1 ribbon-type antisense oligonucleotide (cyclin G1 RiAS) to effectively reduce cyclin G1 expression. Cell viability, in situ terminal deoxyuridine nick end-labeling (TUNEL) assay, flow cytometry, DNA fragmentation, and expression of cell cycle regulatory-related proteins were evaluated by Western blot. Antisense oligonucleotides compromised uterine leiomyoma cell viability and inducted apoptosis in a caspase-independent mechanism. In situ TUNEL and DNA fragmentation revealed apoptosis induction, and fluorescent-activated cell sorting analysis showed increased sub-G1-phase cells. Furthermore, abrogation of cyclin G1 enhanced p53 accumulation, phosphorylation of p53 at Ser-15 residue, and increased expression of cyclin-dependent kinase inhibitors p21 and p27. These data imply that cyclin G1 expression is associated with growth promotion and the potential utility and novelty of using ribbon-type antisense oligonucleotides as a gene therapy strategy to treat human uterine leiomyoma.
- Subjects :
- Cyclin-Dependent Kinase Inhibitor p21
Cell Survival
Cyclin G1
Cyclin D
Blotting, Western
Cyclin B
Apoptosis
Cell Cycle Proteins
DNA Fragmentation
Transfection
Cyclin G
Cell Line, Tumor
Cyclins
In Situ Nick-End Labeling
Tumor Cells, Cultured
Animals
Humans
Viability assay
Cyclin
Uterine leiomyoma
biology
Leiomyoma
Kinase
Caspase 3
Cell Cycle
Obstetrics and Gynecology
Genetic Therapy
Cell cycle
Oligonucleotides, Antisense
Molecular biology
Rats
Uterine Neoplasms
biology.protein
Myometrium
DNA fragmentation
Female
Tumor Suppressor Protein p53
Cyclin-Dependent Kinase Inhibitor p27
Subjects
Details
- ISSN :
- 19337205
- Volume :
- 15
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Reproductive sciences (Thousand Oaks, Calif.)
- Accession number :
- edsair.doi.dedup.....f9986164131b994a8a78d1a6953b9df1