The CD30 gene promoter microsatellite binds transcription factor Yin Yang 1 (YY1) and shows genetic instability in anaplastic large cell lymphoma.
CD30 is a member of the TNF receptor family. Our interest lies in understanding the control of CD30 expression, particularly as its over-expression provides a diagnostic marker for a subset of non-Hodgkin's lymphomas, particularly anaplastic large cell lymphoma (ALCL), and because anti-CD30 treatment has been shown to be efficacious. We have identified a number of regulatory regions, including an Sp1 element in the minimal promoter, and a downstream promoter element that is required for start site selection. The discovery of both an activating AP1 site and an upstream microsatellite that represses transcriptional activity of CD30 suggests that this region is involved in dysregulation of CD30 expression. We have now identified the major microsatellite binding activity as transcription factor Yin Yang 1 by both one-hybrid cDNA library screening and peptide mass fingerprinting. Due to the strong repressive effect of the microsatellite, we also investigated whether microsatellite instability may induce changes in CD30 expression and hence explain the over-expression of CD30 in ALCL. Laser capture microdissection of ALCL biopsies and CD30 microsatellite typing indicated that the neoplastic cells show a high degree of variation, but this does not correlate with high CD30 expression seen in ALCL.
Franchina
M
M
Western Australian Institute for Medical Research & Centre for Medical Research, The University of Western Australia, Crawley, Western Australia.
Woo
A J
AJ
Dods
J
J
Karimi
M
M
Ho
D
D
Watanabe
T
T
Spagnolo
D V
DV
Abraham
L J
LJ
D001483:Base Sequence; D024202:Electrophoretic Mobility Shift Assay / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D006801:Humans; D017730:Ki-1 Antigen / Q000235:genetics* / Q000378:metabolism; D017728:Lymphoma, Large-Cell, Anaplastic / Q000235:genetics* / Q000378:metabolism; D053842:Microsatellite Instability; D018895:Microsatellite Repeats / Q000235:genetics*; D008969:Molecular Sequence Data; D010449:Peptide Mapping / Q000379:methods; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D050986:YY1 Transcription Factor / Q000235:genetics* / Q000378:metabolism
D017730:Ki-1 Antigen; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D050986:YY1 Transcription Factor