Characterization of changes in gene expression associated with malignant transformation by the NF-kappaB family member, v-Rel.
In this study, alterations in gene expression patterns have been examined in v-Rel-transformed avian bone marrow cells. Using a conditional v-Rel estrogen receptor chimera (v-RelER) which transforms cells in an estrogen-dependent manner, we constructed subtraction cDNA libraries from v-RelER-transformed bone marrow cells. Several different sequences were identified whose expression was altered upon hormone activation of v-RelER. These include two genes related to the MIP-1 chemokine family (mip-1beta and a tca3 homologue), a cell surface antigen sca-2 and the transcription factor nfkb1. The expression of each gene was assayed in a number of wild-type and mutant v-Rel-expressing fibroblast and hematopoietic cells. All v-Rel-transformed hematopoietic cells tested express high levels of nfkb1 and sca-2. In fibroblasts, wild-type v-Rel induced expression of mip-1beta and nfkb1, while nontransforming mutants of v-Rel failed to do so, suggesting a role for these two genes in v-Rel mediated transformation. Finally, these genes are expressed at high levels in cells overexpressing wild-type and truncated forms of c-Rel, implying that v-Rel transforms, in part, by induction of c-Rel target genes.
Petrenko
O
O
Department of Microbiology, State University of New York at Stony Brook, 11794, USA.
Ischenko
I
I
Enrietto
P J
PJ
D000818:Animals; D001483:Base Sequence; D001854:Bone Marrow Cells / Q000473:pathology; D002471:Cell Transformation, Neoplastic; D002642:Chick Embryo; D005347:Fibroblasts; D015972:Gene Expression Regulation, Neoplastic; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000502:physiology; D020572:Oncogene Proteins v-rel; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D015682:Retroviridae Proteins, Oncogenic; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic
D016328:NF-kappa B; D020572:Oncogene Proteins v-rel; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D015682:Retroviridae Proteins, Oncogenic; D014157:Transcription Factors