RRC ID 42713
Author Abe H, Shibata MA, Otsuki Y.
Title Caspase cascade of Fas-mediated apoptosis in human normal endometrium and endometrial carcinoma cells.
Journal Mol. Hum. Reprod.
Abstract Human endometrial epithelial cells undergo apoptosis immediately before the menstrual period. Apoptotic signalling was analysed using human endometrial tissue and a human endometrial carcinoma cell line (HHUA). Activity levels of caspase-3, -8, and -9 were elevated in human endometrium during the late secretory phase and in HHUA cells incubated with an anti-Fas monoclonal antibody (mAb). Fas-mediated apoptosis of HHUA cells was blocked by prior exposure to inhibitors of caspase-9, -8 and -3. In HHUA cells treated with anti-Fas mAb, a release of cytochrome c was detected in the cytosolic fraction, in addition a full-length Bid was degraded. Full-length FLIP(L) (p55) was degraded during apoptosis, and p29 (regarded as the product of p55 cleavage) appeared instead of FLIP(L). In normal human endometrial tissue, Bid degradation was also observed in a cyclic manner with a peak during the early secretory phase of the menstrual cycle. Furthermore, the release of cytochrome c was seen in the early secretory phase. However, expression of FLIP(S) was only observed during the menstrual cycle in normal endometrial tissue. We concluded that the main apoptotic signalling in both normal human endometrial tissue and HHUA cells exposed to anti-Fas mAb is the mitochondrial pathway via Bid degradation. Although the function of FLIP is still unknown on normal endometrial tissue, it may be regulated by FLIP(L) expression on HHUA cells derived from human endometrial carcinoma.
Volume 12(9)
Pages 535-41
Published 2006-9
DOI 10.1093/molehr/gah260
PII gah260
PMID 16870953
MeSH Adult Amino Acid Chloromethyl Ketones / pharmacology Antibodies, Monoclonal Apoptosis* / drug effects BH3 Interacting Domain Death Agonist Protein / metabolism CASP8 and FADD-Like Apoptosis Regulating Protein Caspase Inhibitors Caspases / metabolism* Cell Line, Tumor Cell Proliferation / drug effects Cysteine Proteinase Inhibitors / pharmacology Cytochromes c / metabolism DNA Fragmentation Dose-Response Relationship, Drug Endometrial Neoplasms / metabolism* Endometrial Neoplasms / pathology Endometrium / cytology Endometrium / drug effects Endometrium / metabolism* Epithelial Cells / drug effects Epithelial Cells / metabolism Estradiol / pharmacology Female Humans Immunohistochemistry Intracellular Signaling Peptides and Proteins / metabolism Menstrual Cycle / metabolism Middle Aged Progesterone / pharmacology Receptors, Tumor Necrosis Factor / immunology Receptors, Tumor Necrosis Factor / metabolism* Reverse Transcriptase Polymerase Chain Reaction Signal Transduction* / drug effects Time Factors fas Receptor
IF 3.396
Times Cited 22
Human and Animal Cells