| Characterization of the interleukin-1beta-converting enzyme/ced-3-family protease, caspase-3/CPP32, in Hodgkin's disease: lack of caspase-3 expression in nodular lymphocyte predominance Hodgkin's disease. | |
| | |
MedLine Citation:
|
PMID: 10329597 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Apoptosis (programmed cell death) serves an important role in the normal morphogenesis, immunoregulation, and homeostatic mechanisms in both normal and neoplastic cells. Caspase-3/CPP32, a member of the ICE/Ced-3-family of cysteine proteases, is an important downstream mediator of several complex proteolytic cascades that result in apoptosis in both hematopoietic and nonhematopoietic cells. Previous studies have demonstrated that caspase-3 is commonly expressed in classical Hodgkin's disease (CHD); however, the biological significance of its expression in Hodgkin's disease is unknown. In this report, the expression of caspase-3 in nodular lymphocyte predominance Hodgkin's disease (NLPHD) was evaluated by immunohistochemistry; in addition, we investigated the role of caspase-3 in CD95 (Fas)-mediated apoptosis in three CHD cell lines. Formalin-fixed, paraffin-embedded tissue sections from 11 cases of NLPHD were immunostained for caspase-3 using a polyclonal rabbit antibody that detects both the 32-kd zymogen and the 20-kd active subunit of the caspase-3 protease. Only 1/11 cases of NLPHD demonstrated caspase-3 immunopositivity in lymphocytic/histiocytic cells. Caspase-3 expression was also evaluated in three CHD cell lines, HS445, L428, and KMH2. Whereas caspase-3 expression was detected in HS445 and L428 cell lines, no expression was found in KMH2 cells by immunohistochemical staining. Treatment of HS445 and L428 cell lines for 72 hours with agonistic CD95 monoclonal antibody induced marked apoptosis that was significantly inhibited by pretreatment with the caspase-3 inhibitor, DEVD-FMK, as determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay and flow cytometric analysis of 7-amino-actinomycin D staining. In addition, a significant increase in caspase-3 activity as determined by an enzyme colorimetric assay was detected in HS445 and L428 cells after 48 hours of CD95 stimulation. In marked contrast, treatment of caspase-3-deficient KMH2 cells with anti-CD95 mAb did not demonstrate an increase in caspase-3 activity or induce apoptosis. These data demonstrate caspase-3 is important for CD95-mediated apoptosis in CHD cell lines. In addition, the majority of NLPHD cases examined in this study failed to express detectable levels of caspase-3, suggesting these tumor cells may be resistant to apoptotic stimuli dependent on caspase-3 activity. Furthermore, these data suggest the differential expression of caspase-3 noted between NLPHD and CHD may provide additional evidence that each is a unique disease entity. |
| | |
Authors:
|
K F Izban; T Wrone-Smith; E D Hsi; B Schnitzer; M E Quevedo; S Alkan |
Related Documents
:
|
17714487 - Caspase-dependent apoptosis of the hct-8 epithelial cell line induced by the parasite g... 9620337 - Fas-mediated apoptosis in mouse hepatocytes involves the processing and activation of c... 16026317 - Structure and function of poly(adp-ribose) polymerase-1: role in oxidative stress-relat... 11526447 - Poly(adp-ribose) polymerase inhibitors attenuate necrotic but not apoptotic neuronal de... 10627707 - Coculture system to assess biocompatibility of candidate orthopaedic materials. 18940937 - Development of factors to convert frequency to rate for beta-cell replication and apopt... |
Publication Detail:
|
Type: Journal Article |
Journal Detail:
|
Title: The American journal of pathology Volume: 154 ISSN: 0002-9440 ISO Abbreviation: Am. J. Pathol. Publication Date: 1999 May |
Date Detail:
|
Created Date: 1999-06-03 Completed Date: 1999-06-03 Revised Date: 2009-11-18 |
Medline Journal Info:
|
Nlm Unique ID: 0370502 Medline TA: Am J Pathol Country: UNITED STATES |
Other Details:
|
Languages: eng Pagination: 1439-47 Citation Subset: AIM; IM |
Affiliation:
|
Department of Pathology and Cardinal Bernardin Cancer Center, Loyola University Medical Center, Maywood, Illinois, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Antigens, CD95
/
immunology Caspase 1 / analysis* Caspase 3 Caspases / analysis* Enzyme Precursors / analysis* Hodgkin Disease / enzymology* Humans Immunohistochemistry Immunophenotyping Lymph Nodes / pathology* Lymphocyte Count Tumor Cells, Cultured |
| Chemical | |
Reg. No./Substance:
|
0/Antigens, CD95; 0/Enzyme Precursors; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases; EC 3.4.22.36/Caspase 1 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Molecular genetic alterations in radiation-induced astrocytomas.
Next Document: Detection of translocation t(11;14)(q13;q32) in mantle cell lymphoma by fluorescence in situ hybridi...