Back to Search
Start Over
Impaired death-associated protein kinase-mediated survival signals in 5-fluorouracil-resistant human endometrial adenocarcinoma cells.
- Source :
-
Oncology reports [Oncol Rep] 2012 Jul; Vol. 28 (1), pp. 330-6. Date of Electronic Publication: 2012 Apr 23. - Publication Year :
- 2012
-
Abstract
- A recent study showed that both 5-fluorouracil (5FU)-stimulated apoptosis and Fas-mediated apoptosis in human endometrial adenocarcinoma cells are enhanced by targeted knockdown of endogenous death-associated protein kinase (DAPK) with DAPK small-interfering RNAs. Therefore, we investigated the DAPK survival signals in three 5FU-resistant subclones. DAPK knockdown did not enhance 5FU-stimulated or Fas-mediated apoptosis in any of the three 5FU-resistant subclones, but the subclones acquired resistance to VP16-stimulated cell death that was DAPK-independent. Semi-quantitative flow cytometric analyses showed that there was no differential expression in nine cell surface antigens, including Fas, and six intracellular molecules, including DAPK, that may regulate cell death or survival between the parent cells and 5FU-resistant cells. DAPK mRNA and protein were expressed in the 5FU-resistant subclones at similar levels to the parent cells. These results indicate that acquisition of 5FU-resistance may be accompanied by impairment of common apoptotic signals regulating both DAPK-dependent and DAPK-independent pathways.
- Subjects :
- Adenocarcinoma
Apoptosis
Apoptosis Regulatory Proteins genetics
Calcium-Calmodulin-Dependent Protein Kinases genetics
Cell Line, Tumor
Death-Associated Protein Kinases
Endometrial Neoplasms
Female
Flow Cytometry
Gene Expression Regulation, Neoplastic
Gene Knockdown Techniques
Humans
RNA Interference
Signal Transduction
Transcription, Genetic
Antimetabolites, Antineoplastic pharmacology
Apoptosis Regulatory Proteins metabolism
Calcium-Calmodulin-Dependent Protein Kinases metabolism
Cell Survival drug effects
Drug Resistance, Neoplasm
Fluorouracil pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1791-2431
- Volume :
- 28
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Oncology reports
- Publication Type :
- Academic Journal
- Accession number :
- 22552543
- Full Text :
- https://doi.org/10.3892/or.2012.1774