Immunohistochemical detection of ribosomal transcription factor UBF and AgNOR staining identify apoptotic events in neoplastic cells of Hodgkin's disease and in other lymphoid cells.
Ribosomal RNA synthesis is a key molecular process for understanding the mechanisms that drive cell proliferation. In this process, the upstream binding factor (UBF) is involved in regulating rDNA transcription at the nucleolus, together with RNA polymerase I. Recently, UBF was demonstrated to be a substrate for selective cleavage by specific proteases during apoptosis. Here we studied the expression of UBF in several cases of Hodgkin's disease (HD) by immunostaining and found it to be absent or clearly diminished in a high proportion of Reed-Sternberg cells and Hodgkin cells compared to small reactive lymphocytes. This result contrasted with labeling of those cells by the AgNOR technique, a marker of cell proliferation dependent on increased amounts of several proteins related to ribosome assembly. Disappearance of UBF and preservation of other NOR proteins is consistent with the pattern of selective proteolysis by caspases described in early stages of apoptosis. This correlates well with our results observed on induction of apoptosis in Jurkat cells treated with anti-FAS/APO-1 serum and with those in aged germinal center B-cells, in which UBF was no longer seen although the staining signal of other NOR proteins was maintained. These results support the concept that the rate of apoptosis is higher in neoplastic cells of HD than in the benign reactive lymphocyte population. Differential proteolysis of NOR proteins, as revealed by double staining of UBF and AgNOR, may prove valuable for identification of early stages of apoptosis in cytological and histopathological samples.
Torres-Montaner
A
A
Servicio de Anatomía Patológica, Hospital Universitario de Puerto Real, Cádiz, Spain.
Bolívar
J
J
Astola
A
A
Gimenez-Mas
J A
JA
Brieva
J A
JA
Valdivia
M M
MM
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D006224:Cricetinae; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006689:Hodgkin Disease / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D019169:Jurkat Cells; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008214:Lymphocytes / Q000378:metabolism; D035463:Pol1 Transcription Initiation Complex Proteins; D012270:Ribosomes / Q000235:genetics*; D016622:Silver Staining; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; D035463:Pol1 Transcription Initiation Complex Proteins; D014157:Transcription Factors; C063844:transcription factor UBF