Wilms’ tumor gene <i>WT1</i> 17AA(–)/KTS(–) isoform induces morphological changes and promotes cell migration and invasion <i>in vitro</i>

Jomgeow, Tanyarat; Oji, Yusuke; Tsuji, Naoko; Ikeda, Yoko; Ito, Ken; Tsuda, Asako; Nakazawa, Tsutomu; Tatsumi, N; Sakaguchi, Nobuki; Takashima, S; Shirakata, Toshiaki; Nishida, Sumiyuki; Hosen, Naoki; Kawakami, Manabu; Tsuboi, Akihiro; Oka, Y.; Itoh, Kazuyuki; Sugiyama, Haruo

doi:10.1111/j.1349-7006.2006.00169.x

Cited by 65 publications

(58 citation statements)

References 35 publications

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“…Actin remodelling could be the result of activation of oncogenic signalling pathways, or misexpression of some actin-binding proteins (Rao and Li, 2004). Wt1 was named as one of the proteins implicated in actin cytoskeletal changes in cancer cells (Jomgeow et al, 2006) and cultured podocytes (Viney et al, 2007). In this study, we show that actin remodelling could have a direct influence on the location and regulation of Wt1 functions in the cell.…”

Section: Gfp-hnrnpa1 T7-wt1+/+ Gfp-sf2mentioning

confidence: 59%

Actin: a novel interaction partner of WT1 influencing its cell dynamic properties

et al. 2009

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The Wilms' tumour suppressor, WT1, is a zinc finger protein with key roles in normal development of the genitourinary system and tumourigenesis. Mutations or deletion of WT1 result in a spectrum of developmental disorders and susceptibility to Wilms' tumour in children. Ectopic expression of Wt1 associated with oncogenic functions has been observed in a large number of malignancies, including haematological and solid cancers. Although Wt1 is predominantly a nuclear protein in normal tissues, it is mostly cytoplasmic in the majority of Wt1-expressing tumours. Actin was identified in this study as a new WT1 interaction partner both in the nucleus and in the cytoplasm. We confirmed this interaction both in vitro and in vivo and started to explore its functional significance. Perturbation of the actin cytoskeleton moved Wt1 off the polysome fraction in the cytoplasm, cancelled its nucleo-cytoplasmic shuttling and altered Wt1 DNAand RNA-binding abilities. These data have implications for Wt1 functions in relation to RNA metabolism and response to cytoskeletal alterations in cancer cells. Thus, our findings could shed more light on the functions of both these proteins and possibly pave way for the development of new cancer therapies.

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Section: Gfp-hnrnpa1 T7-wt1+/+ Gfp-sf2mentioning

confidence: 59%

Actin: a novel interaction partner of WT1 influencing its cell dynamic properties

et al. 2009

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“…Thus, it is likely that the high relative levels of Wt1 ( þ KTS) isoforms in breast cancer cell lines contribute to the pro-proliferative effects of Wt1 in breast cancer cells, and consequently to a role as a potential breast oncogene. This does not, however, exclude a role for the other isoforms, as indicated by the recent observation that overexpression of the Wt1 (À/À) isoform may increase motility and invasion in ZR-75 and SKBr3 breast cancer cells (Jomgeow et al, 2006). More commonly however, overexpression of the Wt1 (À/À) isoform has been observed to have tumor suppressor effects in mammary epithelial cells (Reizner et al, 2005;Burwell et al, 2007).…”

Section: Discussionmentioning

confidence: 86%

Wilms' tumor protein 1: an early target of progestin regulation in T-47D breast cancer cells that modulates proliferation and differentiation

et al. 2007

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Progesterone regulates the proliferation and differentiation of normal mammary epithelium. In breast cancer cells, progesterone and its synthetic analogs, progestins, induce long-term growth inhibition and differentiation. However, the mechanisms responsible are not fully understood. When T-47D breast cancer cells were treated with the synthetic progestin ORG 2058 (16a-ethoxy-21-hydroxy-19-norpregn-4-en-3,20-dione), all isoforms of Wilms' tumor protein 1 (Wt1) mRNA and protein were rapidly downregulated. We reasoned that the decrease in Wt1 levels may contribute to the long-term antiproliferative and differentiative effects of progestins as proliferation and differentiation are known end points of Wt1 action. Consistent with this idea, Wt1 small interfering RNA led to a decrease in S phase and cyclin D1 levels, and increased Oil-Red-O staining, indicating increased lipogenesis. Conversely, overexpression of Wt1 attenuated the decrease in S phase induced by ORG 2058 at 48-96 h. This was accompanied by the sustained expression of cyclin D1 despite progestin treatment, and increased levels of retinoblastoma (Rb) phosphorylation at sites targeted by cyclin D1-Cdk4 (Ser249/Thr252). Wt1 overexpression also attenuated the ORG 2058-mediated increase in fatty acid synthase levels and reduced lipogenesis. Thus, Wt1 downregulation was sufficient to mimic the effects of progestin and was necessary for complete progestinmediated proliferative arrest and subsequent differentiation. Furthermore, Wt1 overexpression modulated the effects of progestins but not anti-estrogens or androgens. These results indicate that Wt1 is an important early target of progestins that regulates both proliferation and differentiation in breast cancer cells.

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“…15,34 Functional studies suggest that many of WT1 effects are related to particular WT1 isoforms. 8,20,[35][36][37][38][39][40] The available data on WT1 isoform expression patterns in normal and malignant hematopoiesis are scarce and the methods so far used for the detection of WT1 major isoforms (reverse transcriptase PCR, GeneScan, quantitative PCR of EX5[ þ ] and KTS[ þ ] variants) have only yielded an approximate estimation of WT1 isoform levels.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2012

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Wilms' tumor gene 1 (WT1) functions including some contradictory effects may be explained by the presence and interactions of its isoforms, however, their evaluation has been so far complicated by several technical problems. We designed unique quantitative PCR systems for direct quantification of the majorand verified their sensitivity, specificity and reproducibility in extensive testing. With this method we evaluated WT1 total and isoform expression in 23 normal bone marrow (BM) samples, 73 childhood acute myeloid leukemia (AML), 20 childhood myelodysplastic syndrome (MDS), 9 childhood severe aplastic anemia (SAA), 30 adult AML and 29 adult MDS patients. WT1 isoform patterns showed differences among these samples and clustered them into groups representing the specific diagnoses (Po0.0001). Isoform profiles were independent of total WT1 expression and possess certain common features-overexpression of isoform D and

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Wilms’ tumor gene WT1 17AA(–)/KTS(–) isoform induces morphological changes and promotes cell migration and invasion in vitro

Cited by 65 publications

References 35 publications

Actin: a novel interaction partner of WT1 influencing its cell dynamic properties

Actin: a novel interaction partner of WT1 influencing its cell dynamic properties

Wilms' tumor protein 1: an early target of progestin regulation in T-47D breast cancer cells that modulates proliferation 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

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