WT1 proteins: functions in growth and differentiation

Real-time PCR quantification of major Wilms’ tumor gene 1 (WT1) isoforms in acute myeloid leukemia, their characteristic expression patterns and possible functional consequences

“…Wilms' tumor gene 1 (WT1) has been intensively studied because of its important role in embryogenesis and oncogenesis, as a potential new prognostic factor, minimal residual disease marker and target of vaccination immunotherapy in various malignancies, particularly in acute myeloid leukemia (AML; reviewed [1][2][3][4][5][6][7]. Although there is an increasing number of genes and signaling pathways WT1 has been shown to interact with, the actual relevance and input of WT1 to the malignant process has yet to be elucidated.…”

“…It activates or more often represses the transcription of many target genes involved in the cell cycle, proliferation, differentiation and apoptosis control, and is also involved in post-transcriptional mRNA processing. 3,[10][11][12] At least 36 isoforms of WT1 protein are produced from the same DNA template as a result of alternative transcription initiation, alternative pre-mRNA splicing, mRNA editing and alternative translation initiation. 1,3,5,10,[13][14][15][16][17][18] The four major WT1 isoforms are generated by an alternative splicing and vary in the presence or absence of so called 17AA insert (17 amino acids encoded by the whole exon 5) and KTS insert (according to the three amino acids leucinethreonine-serine encoded by the terminal sequence of exon 9)- [19][20][21][22][23] An alternative WT1 transcript, AWT1 (also short transcript, sWT1), maintains WT1 exonic structure between exons 2 and 10 but uses another first exon located in intron 1 of WT1 (exon 1a).…”

“…The AWT1 transcript does not contain the repression domain ( Figure 1). 1,3,14,15,26,27 Isoforms containing both splice inserts are the prevalent variants, the least common transcripts are those missing both inserts, and the physiological ratio of A[…”

Immunohistochemical detection of WT1 protein in a variety of cancer cells

“…The WT1 gene encodes a transcription factor with four DNA-binding zinc fingers at the C terminus. 1,2,7 In vitro studies showed that WT1 suppresses or activates a number of genes, including those for PDGF-A chain, EGF receptor, CSF-1, IGF-II, IGF-I receptor, RAR-a, c-myc, bcl-2, and WT1 itself. 7,8 In embryonic life, WT1 plays a critical role in the development of the genitourinary tract, spleen, and mesothelial structures.…”

“…1,2,7 In vitro studies showed that WT1 suppresses or activates a number of genes, including those for PDGF-A chain, EGF receptor, CSF-1, IGF-II, IGF-I receptor, RAR-a, c-myc, bcl-2, and WT1 itself. 7,8 In embryonic life, WT1 plays a critical role in the development of the genitourinary tract, spleen, and mesothelial structures. 3,4,9 In normal adult tissue, it is expressed in mesothelium, glomerular podocytes and mesangial cells of the kidney, CD34-positive hematopoietic stem cells, Sertoli cells of the testis, stromal cells, surface epithelium and granulosa cells of the ovary, and myometrium and endometrial stromal cells of the uterus.…”