Expression of bcl-2 protein and transcription of the Epstein-Barr virus bcl-2 homologue BHRF-1 in Hodgkin's disease: implications for different pathogenic mechanisms.
Epstein-Barr virus (EBV) is frequently found in Hodgkin and Reed-Sternberg cells in Hodgkin's disease. Epstein-Barr virus has transforming properties in vitro and might be involved in the pathogenesis of certain types of Hodgkin's disease. One of the possible mechanisms is the upregulation of the human proto-oncogene bcl-2 by the latent membrane protein 1 of EBV in vitro. Another possibility might be the expression of the viral 'bcl-2 homologue' BHRF-1. In the present study of 64 cases of Hodgkin's disease we investigated the expression of bcl-2 at the protein level in relation to the presence of EBV. Moreover, in 10 EBV positive cases we investigated, the expression of the bcl-2 homologue, BHRF-1, by reverse-transcriptase PCR. bcl-2 was detected in 14 of 22 (64%) EBV positive and in 37 of 42 (88%) EBV negative cases. In 17 of 22 (77%) EBV positive cases Reed-Sternberg cells were negative (n = 8) or expressed the bcl-2 protein in a very low percentage ( < 5%) of cells (n = 9), whereas in 20 of 42 (43%) of the EBV negative cases the majority ( > 50%) of the neoplastic cells were bcl-2 positive. Using the reverse-transcriptase PCR with primers amplifying transcripts of BHRF-1 we were able to detect BHRF-1 transcripts in only one of the 10 tested cases of EBV positive Hodgkin's disease. Our data indicate that in EBV positive Hodgkin's disease growth advantage of Reed-Sternberg cells is not obtained by upregulation of bcl-2 or by the EBV homologue BHRF-1.
Jiwa
N M
NM
Department of Pathology, Free University Hospital, Amsterdam, The Netherlands.
Oudejans
J J
JJ
Bai
M C
MC
Van den Brule
A J
AJ
Horstman
A
A
Vos
W
W
Van der Valk
P
P
Kluin
P M
PM
Walboomers
J M
JM
Meijer
C J
CJ
D001483:Base Sequence; D015972:Gene Expression Regulation, Neoplastic; D004854:Herpesvirus 4, Human / Q000302:isolation & purification*; D006689:Hodgkin Disease / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D006801:Humans; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2; D012367:RNA, Viral / Q000032:analysis; D016539:Reed-Sternberg Cells / Q000378:metabolism*; D015854:Up-Regulation; D014763:Viral Matrix Proteins / Q000235:genetics; D014764:Viral Proteins / Q000032:analysis / Q000235:genetics*
C083278:BHRF1 protein, Human herpesvirus 4; C037662:EBV-associated membrane antigen, Epstein-Barr virus; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012367:RNA, Viral; D014763:Viral Matrix Proteins; D014764:Viral Proteins