WT1 contributes to leukemogenesis: expression patterns in 7,12-dimethylbenz[a]anthracene (DMBA)-induced leukemia.
The Wilms'-tumor gene WT1 may have a different function from a tumor-suppressor gene in some leukemias. Using the 7,12-dimethylbenz[a]anthracene (DMBA)-induced rat leukemia system, we examined whether WT1 expression was involved during leukemogenesis, since this model enabled us to analyze cells altered by DMBA at various stages of leukemogenesis. By the semi-quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) method, WT1 expression was detected in 15 (71%) of 21 DMBA-induced erythroblastic leukemias. Among 15 WT1-expressing leukemias, GATA-1, which is an erythroid-specific transcription factor and might regulate WT1 expression, was also expressed in 13 cases (p < 0.05). On the other hand, WT1 expression was not detected in any normal or early pre-leukemic rats and was detected in 1 of 8 rats in late pre-leukemic stages. These results showed that cells with a high expression level of WT1 tended to develop into leukemia and that WT1 contributed to leukemogenesis in the late stage, suggesting that the expression of WT1 plays an important role in cell proliferation and in maintaining the viability of some leukemia cells.
Osaka
M
M
Department of Pathology, Faculty of Medicine, Kyoto University, Japan. osaka@med.kyoto-u.ac.jp
Koami
K
K
Sugiyama
T
T
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity*; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D003043:Cocarcinogenesis; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D050981:Erythroid-Specific DNA-Binding Factors; D005260:Female; D050982:GATA1 Transcription Factor; D015973:Gene Expression Regulation, Leukemic / Q000502:physiology; D016162:Genes, Wilms Tumor / Q000187:drug effects*; D011905:Genes, ras; D004915:Leukemia, Erythroblastic, Acute / Q000139:chemically induced* / Q000235:genetics* / Q000378:metabolism; D008297:Male; D009154:Mutation; D016133:Polymerase Chain Reaction; D051381:Rats; D011919:Rats, Inbred Strains; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D014158:Transcription, Genetic; D025721:WT1 Proteins
D002273:Carcinogens; D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; C494690:Gata1 protein, rat; D014157:Transcription Factors; D025721:WT1 Proteins; D015127:9,10-Dimethyl-1,2-benzanthracene