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Radiation-induced cell death is independent of the apoptotic signals mediated by death-associated protein kinase in human cervical squamous cell carcinoma cells.
- Source :
-
Oncology reports [Oncol Rep] 2005 Oct; Vol. 14 (4), pp. 949-55. - Publication Year :
- 2005
-
Abstract
- Death-associated protein kinase (DAPK) was originally identified as a positive mediator of interferon-gamma (IFNgamma)-induced apoptosis in cervical cancer cells, and interferons have been reported to enhance radiosensitivity in various types of squamous cell carcinoma. To examine whether DAPK can regulate cancer cell radiosensitivity, we investigated DAPK expression and radiosensitivity in human cancer cell lines, including the cervical squamous cell carcinoma cell line, ME180, which is both radiosensitive and IFNgamma-sensitive. Of the 5 human cancer cell lines examined, ME180 cells were the most radiosensitive, but their level of DAPK protein expression was undetectable by western blotting. A comparative study of ME180 cells with 2 other uterine cancer cell lines, HHUA and HOKUG, revealed no significant relationships between cellular radiosensitivity and DAPK protein expression or hypermethylation of the DAPK promoter CpG island. INFgamma dose-dependently inhibited ME180 cell proliferation, but did not induce any cell death. IFNgamma significantly enhanced the radiosensitivity of ME180 cells with a slight increase in DAPK protein expression, while irradiation significantly reduced their sensitivity to the growth-inhibitory signals of INFgamma. Analyses of 6 monoclonal cisplatin-resistant subclones established from ME180 cells revealed that all 6 were significantly more radioresistant than the parent ME180 cells without any change in the DAPK protein expression. These results indicate that DAPK does not regulate radiation-induced cell death and that it cannot be either a target molecule for radiotherapy with gene therapy or a prognostic marker for cervical cancer patients treated with radiotherapy.
- Subjects :
- Antineoplastic Agents pharmacology
Apoptosis Regulatory Proteins
Blotting, Western
Cell Line, Tumor
Cell Survival
Cisplatin pharmacology
CpG Islands
DNA metabolism
DNA Methylation
Death-Associated Protein Kinases
Dose-Response Relationship, Radiation
Electrophoresis, Agar Gel
Female
HeLa Cells
Humans
Mass Spectrometry
Polymerase Chain Reaction
Promoter Regions, Genetic
Radiation
Radiation Tolerance
Sulfites pharmacology
Apoptosis
Calcium-Calmodulin-Dependent Protein Kinases metabolism
Carcinoma, Squamous Cell pathology
Interferon-gamma metabolism
Uterine Cervical Neoplasms pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1021-335X
- Volume :
- 14
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Oncology reports
- Publication Type :
- Academic Journal
- Accession number :
- 16142356