Overexpression of the Wilms' tumor gene WT1 in de novo lung cancers

Abstract

Expression of theThe Wilms' tumor gene WT1 was originally isolated as a tumorsuppressor gene responsible for Wilms' tumor, a kidney neoplasm of childhood. 1 However, we proposed that WT1 played an oncogenic role in leukemogenesis based on the following findings: 2 (i) the wild-type WT1 gene was expressed at high levels in leukemic blast cells, 3,4 (ii) there was a clear and inverse correlation between WT1 expression levels and prognosis in acute leukemia, 3 (iii) WT1 expression increased at relapse of acute leukemia, 5 (iv) growth of leukemic blast cells was inhibited by the treatment of WT1 antisense oligomers 6 and (v) constitutive expression of WT1 blocked differentiation and instead induced proliferation in response to granulocyte colony-stimulating factor in 32D cl3 myeloid progenitor cells 7 and normal myeloid progenitor cells. 8 Furthermore, we demonstrated that the wild-type WT1 as expressed in various types of cell line derived from lung cancer, gastric cancer, colon cancer and breast cancer and that growth of these WT1-expressing tumor cells was inhibited by the treatment of WT1 antisense oligomers. 9 These data suggested an oncogenic role of the WT1 gene in tumorigenesis. However, the involvement of the WT1 gene in de novo solid tumors remained unclear. In the present study, we examined WT1 expression in de novo lung cancer using quantitative real-time RT-PCR and immunohistochemistry and demonstrated that the wild-type WT1 was overexpressed in 54/56 (96%) de novo non-small cell lung cancers (NSCLCs) and 5/6 (83%) de novo small cell lung cancers (SCLCs) examined.

Immunohistochemical detection of WT1 protein in a variety of cancer cells

“…Oji et al showed overexpression of WT1 mRNA in cell lines derived from various cancers and their primary tumors. 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.…”

“…However, immunohistochemical data on WT1 expression in other types of cancers are either lacking or conflicting. 17,18,[21][22][23][24] As for staining patterns, cytoplasmic staining has been regarded as nonspecific and not been counted as positive in most previous reports. Therefore, the cytoplasmic staining of WT1 had not been evaluated in most types of tumors until now.…”

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

“…[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. 43,44 It is therefore a target for gene therapy with high potential for lung cancer treatment.…”

Upregulation of Wilms' tumor gene 1 (WT1) in desmoid tumors

“…The mechanism of this upregulation is as yet unclear, as is the case for other tumors in the literature shown to contain elevated levels of WT1. 13,14 Our findings of WT1 overexpression in tumoral fibroblasts add to the growing spectrum of mainly epithelial tumors containing high levels of WT1. The exact role of WT1 in tumorigenesis remains to be elucidated.…”

“…WT1 is expressed at high levels not only in most types of leukemia but also in various types of solid tumors, including lung and breast cancer. 13,14 Some reports suggested that deregulation of the Wnt signaling pathway plays a role in the genesis of some Wilms' tumors. One group reported ␤-catenin mutations in 21 of 153 (14%) Wilms' tumors 9 confirming an earlier observation showing ␤-catenin mutations in 6 of 40 (15%) Wilms' tumors.…”