[The proteasome and malignant hemopathies].
Proteasomes are the main non lysosomal proteolytic structures of the cells. They correspond to the major system eliminating abnormal proteins, short half-life proteins and proteins controlling the cell cycle. They are essential for the production of peptides subsequently presented by the MHC-I. They are formed by a proteolytic core (the 20S proteasome) made of 4 rings of 7 proteic subunits associated with regulatory complexes (namely the 19S complex forming the 26S proteasome). Using classical cell biology techniques (cytometry, immunofluorescence microscopy, Western blot) our group has particularly studied the proteasome expression of leukaemic cell lines (U937 and CCRF-CEM) during in vitro differentiation induced by PMA and Vitamin D plus retinoïc acid. During differentiation, the level of proteasome expression and its localization vary. The various monoclonal antibodies used provided different patterns according to the different subunits. There was a general trend to a disappearance of nuclear proteasome and to a decrease in their cytoplasmic expression. In contrast, proteosomal antigens were increased on the cell membrane and in culture supernatants. We derived an ELISA test to measure plasma proteasome concentrations. Preliminary results showed differences between patients with haemopoietic malignancies or solid tumors and normal donors. Proteasome levels varied under treatment. They were correlated with LDH levels. Taken together, these results argue in favor of a role for cellular proteasomes in malignant differentiation process, and emphasize the qualitative changes in proteasome expression. Plasma proteasomes do not only reflect tumor cell mass and could play a role in addition to their proteolytic activity. They seem to be a relevant tool for diagnosis, prognosis and therapeutic monitoring.
Lavabre-Bertrand
T
T
Laboratoire de Biologie Cellulaire et de Cytogénétique Moléculaire. Faculté de Médecine de Montpellier-Nimes, France. t-lavabre@usa.net
Henry
L
L
Guiraud
I
I
Carillo
S
S
Bureau
J P
JP
D014408:Biomarkers, Tumor / Q000097:blood; D002454:Cell Differentiation / Q000187:drug effects; D002462:Cell Membrane / Q000201:enzymology; D002467:Cell Nucleus / Q000201:enzymology; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000097:blood / Q000502:physiology* / Q000648:ultrastructure; D003593:Cytoplasm / Q000201:enzymology; D004797:Enzyme-Linked Immunosorbent Assay; D019337:Hematologic Neoplasms / Q000097:blood / Q000201:enzymology* / Q000473:pathology / Q000648:ultrastructure; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000097:blood; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000201:enzymology / Q000473:pathology; D009097:Multienzyme Complexes / Q000097:blood / Q000502:physiology* / Q000648:ultrastructure; D009363:Neoplasm Proteins / Q000378:metabolism*; D009369:Neoplasms / Q000097:blood / Q000201:enzymology; D046988:Proteasome Endopeptidase Complex; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology; D020298:U937 Cells / Q000187:drug effects / Q000201:enzymology; D014807:Vitamin D / Q000494:pharmacology
D014408:Biomarkers, Tumor; D009097:Multienzyme Complexes; D009363:Neoplasm Proteins; D014807:Vitamin D; D014212:Tretinoin; D007770:L-Lactate Dehydrogenase; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D013755:Tetradecanoylphorbol Acetate