Expression of the Wilms' Tumor Gene <i>WT1</i> in Solid Tumors and Its Involvement in Tumor Cell Growth

Oji, Yusuke; Ogawa, Hiroyasu; Tamaki, Hiroya; Oka, Y.; Tsuboi, Akihiro; Kim, Eui Ho; Soma, Toshihiro; Tatekawa, Toyoshi; Kawakami, Manabu; Asada, Masaki; Kishimoto, Tadamitsu; Sugiyama, Haruo

doi:10.1111/j.1349-7006.1999.tb00733.x

Cited by 196 publications

(176 citation statements)

References 39 publications

(24 reference statements)

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“…22,24,30,35 They also demonstrated that the growth of WT1-expressing cancer cells was inhibited by treatment with WT1 antisense oligomers. 13,14 These findings suggest that WT1 plays an important role in the carcinogenesis of various cancers.…”

Section: Discussionmentioning

confidence: 95%

“…The histologic diagnosis of each tumor was confirmed on the hematoxylin and eosin-stained sections: there were 13 Table 1.…”

Section: Specimensmentioning

confidence: 99%

“…WT1 mRNA is overexpressed in several kinds of hematological malignancies, and quantitative detection of its expression could be useful for monitoring minimal residual disease in case of leukemia. [10][11][12] Furthermore, recent studies showed the overexpression of WT1 mRNA in various kinds of solid tumors, 13 the growth inhibition of WT1-expressing cells by WT1 antisense oligomers, 13,14 and a correlation between a high level of WT1 and a poor prognosis in patients with certain kinds of tumors. 12,15 These findings suggest that WT1 plays an oncogenic rather than tumor-suppressive role in human cancers.…”

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confidence: 99%

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Immunohistochemical detection of WT1 protein in a variety of cancer cells

et al. 2006

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WT1 was first identified as a tumor suppressor involved in the development of Wilms' tumor. Recently, oncogenic properties of WT1 have been demonstrated in various hematological malignancies and solid tumors. Because WT1 has been identified as a molecular target for cancer immunotherapy, immunohistochemical detection of WT1 in tumor cells has become an essential part of routine practice. In the present study, the expression of WT1 was examined in 494 cases of human cancers, including tumors of the gastrointestinal and pancreatobiliary system, urinary tract, male and female genital organs, breast, lung, brain, skin, soft tissues and bone by immunohistochemistry using polyclonal (C-19) and monoclonal (6F-H2) antibodies against WT1 protein. Staining for C-19 and 6F-H2 was found in 35-100 and 5-88% of the cases of each kind of tumor, respectively. WT1-positive tumors included tumor of the stomach, prostate, and biliary and urinary systems, and malignant melanomas. A majority of the positive cases showed diffuse or granular staining in the cytoplasm, whereas ovarian tumors and desmoplastic small round cell tumors frequently showed nuclear staining. Glioblastomas, some of soft tissue sarcomas, osteosarcomas, and malignant melanomas of the skin showed extremely strong cytoplasmic staining as compared with other tumors. Western blot analysis showed that WT1 protein was predominantly expressed in the cytoplasm of the tumor cells in two cases of lung adenocarcinoma, supporting the intracytoplasmic staining for WT1 using immunohistochemistry. Immunohistochemical detection with routinely processed histologic sections could provide meaningful information on the expression of WT1 in cancer cells.

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Section: Discussionmentioning

confidence: 95%

“…The histologic diagnosis of each tumor was confirmed on the hematoxylin and eosin-stained sections: there were 13 Table 1.…”

Section: Specimensmentioning

confidence: 99%

mentioning

confidence: 99%

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Immunohistochemical detection of WT1 protein in a variety of cancer cells

et al. 2006

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“…WT1-transfected cells maintain the features of undifferentiated cells and continue to proliferate. Oji et al 24 have also shown that in other tumor cell lines including gastric, lung and ovarian cancer cell lines, cell growth is inhibited by treatment with WT1 antisense oligo-nucleotides, suggesting that in these cell backgrounds WT1 expression is oncogenic. We cannot rule out this possibility in neural tumors until a quantitative analysis of WT1 expression has been done.…”

Section: Discussionmentioning

confidence: 98%

Expression and mutation analysis of the Wilms' tumor 1 gene in human neural tumors

Dennis

Manji

Carrington

et al. 2001

Intl Journal of Cancer

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The Wilms' tumor 1 gene, WT1, encodes a zinc-finger protein that is implicated in the development of Wilms' tumor. Mutant or aberrantly expressed WT1 isoforms have also been described in desmoplastic small round cell tumor, acute leukemias, mesothelioma, breast tumors and melanoma. During early development, WT1 is expressed in the brain and spinal cord, however its role in the malignancies that affect these tissues has not been previously investigated. In our study we have examined neural tumors including brain tumors and neuroblastomas for WT1 expression and for mutations affecting the zinc-fingers. Although WT1 expression was detected in gliomas, medulloblastomas and neuroblastomas, neither zinc-finger region mutations nor splicing anomalies affecting the KTS site were detected. We therefore conclude that WT1 does not play a significant role in the etiology of human neural tumors.

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“…It also plays an important role in cell proliferation, differentiation of various tissue types, and apoptosis. [40][41][42] Increased expression of WT1 is associated with unfavorable prognosis of multiple malignancies and its downregulation by different gene therapy strategies leads to a down of cell proliferation and apoptosis. [32][33][34][35] Overexpression of WT1 mRNA has been detected in 54 of 56 (96%) de novo non-small cell lung cancers and protein overexpression was confirmed in 5 of 6 (83%) de novo small cell lung cancers by immunohistochemistry.…”

Section: Introductionmentioning

confidence: 99%

WT1 gene silencing by aerosol delivery of PEI–RNAi complexes inhibits B16-F10 lung metastases growth

et al. 2009

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The Wilms' tumor gene 1 (WT1) is a universal tumor antigen and consequently a good therapeutic target for the development of gene therapy strategies. Earlier, we reported the in vitro efficacy of WT1 RNAi in the inhibition of B16F10 murine melanoma cell line growth. In this study, we used an aerosol system to deliver WT1 RNAi complexes, polyethyleneimine (PEI)-WT1-1 or PEI-WT1-2, to the lungs of mice with B16F10 lung metastasis. This treatment produced a statistically significant (P ¼ 0.020) reduction in the number and size of lung tumor foci, resulting in decreased lung weight and tumor index in treated mice compared with controls. The WT1 RNAi treatment also reduced the number and size of tumor blood vessels, suggesting decreased angiogenesis. Furthermore, the treated lung tissue showed cells in the tumor infiltrations undergoing apoptosis and elevated expression of the proapoptotic genes Bcl-xS and Bax, suggesting an activation of the intrinsic apoptotic pathway. Overall, WT1-1 treatment prolonged the mean survival time of tumor-bearing mice in comparison with the control and WT1-2-treated mice. Our data show that WT1 gene silencing in vivo by aerosol delivery of PEI-WT1 RNAi complexes is an effective therapeutic strategy for the treatment of lung metastases.

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Expression of the Wilms' Tumor Gene WT1 in Solid Tumors and Its Involvement in Tumor Cell Growth

Cited by 196 publications

References 39 publications

Immunohistochemical detection of WT1 protein in a variety of cancer cells

Immunohistochemical detection of WT1 protein in a variety of cancer cells

Expression and mutation analysis of the Wilms' tumor 1 gene in human neural tumors

WT1 gene silencing by aerosol delivery of PEI–RNAi complexes inhibits B16-F10 lung metastases growth

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