[Involvement of WT1 gene expression in regulation of P53 and MDM2 proteins function in acute lymphoblastic leukemia].
Using sensitive techniques such as reverse transcription polymerase chain reaction (RT-PCR) the expression of WT1 gene in acute lymphoblastic leukemias (ALL) is indicated. High level of mRNA WT1 was only observed in ALL cases with leukemic cells characterized by P53- and MDM2-positive staining in cytometric analysis. The overexpression of P53 protein has not been induced by P53 gene abnormalities and MDM2 protein synthesis was independent from respective gene amplification. The data suggest that WT1 may play a distinct role in the pathophysiology of acute leukemias. It can regulate the function of the main oncoprotein network factors--P53 and MDM2 proteins. There was concluded that the most important mechanism of tissue P53-immunopositivity was connected with the P53 interactions with other oncoproteins, especially with MDM2 and WT1. They have caused different effects in particular cases and several phenotypes of leukemic cells were described. However, the negative tissue staining with anti-P53 monoclonal antibodies can not be evidence of the proper P53 protein function. The immunohistochemical estimations of the P53 level in the cells are insufficient for diagnostic and clinical evaluations. Molecular analyses of P53 and MDM2 genes, as well the WT1 gene transcription, are necessary for the proper characterisation of functional and structural status of P53.
Bartkowiak
J
J
Zakład Biologii Molekularnej Katedry Onkologii Akademii Medycznej w Łodzi.
Wójcik
I
I
Stankiewicz
W
W
D016022:Case-Control Studies; D018076:DNA, Complementary / Q000032:analysis; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D051736:Proto-Oncogene Proteins c-mdm2; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D025721:WT1 Proteins / Q000235:genetics / Q000378:metabolism*
D018076:DNA, Complementary; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D025721:WT1 Proteins; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2