Quantitative and qualitative variation of ETS-1 transcripts in hematologic malignancies.
The ETS family proteins have a conserved DNA-binding domain and act as transcription factors. Three domains have been recently defined in human ETS-1 proteins and their role could depend upon the nature of alternative transcripts according to whether they possess or lack DNA binding and/or transcriptional activation domain and also point mutation that could affect these important domains. Expression of ETS-1 gene is very complex and is controlled at several levels: the initiation of transcription, alternative splicing, post-translational modification, and protein stability. As a selection apparently exists for ETS-1 gene activation in hematopoietic cells, we investigated a relation between quantitative and qualitative ETS-1 expression and leukemogenesis. Using Northern blot, polymerase chain reaction (PCR), and single strand conformation polymorphism (SSCP) methods, we analyzed quantitative and qualitative ETS-1 expression in a variety of hematological pathologies and cell lines of different origin. Two ETS-1 transcripts of 6.8 and 2.7 kb, resulting from differential polyadenylation site utilization and exhibiting different stability, were observed. We identified, in a great number of patients, the four alternative ETS-1 products, but the relative extent significance of the four transcripts was very different from one patient to another. A non-conservative mutation observed in one case of T-cell acute lymphoblastic leukemia (T-ALL) and in the ETS-1 transactivation domain raised the question of suppressor activity for some ETS-1 products, as it is now known that activators and repressors can be encoded by the same gene and consistently co-expressed in vivo.
Collyn d'Hooghe
M
M
U 124 INSERUM, Institut de Recherches sur le Cancer, Lille, France.
Galiègue-Zouitina
S
S
Szymiczek
D
D
Lantoine
D
D
Quief
S
S
Loucheux-Lefebvre
M H
MH
Kerckaert
J P
JP
D001483:Base Sequence; D015152:Blotting, Northern; D015870:Gene Expression; D006801:Humans; D007938:Leukemia / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D050783:Proto-Oncogene Proteins c-ets; D011519:Proto-Oncogenes / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis*; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic; D015533:Transcriptional Activation
C494041:ETS1 protein, human; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D012333:RNA, Messenger; D014157:Transcription Factors