Overexpression of the Wilms' tumor gene WT1 in human bone and soft‐tissue sarcomas

Overexpression of the Wilms' tumor gene WT1 in colorectal adenocarcinoma

“…However, we hypothesized that the WT1 gene plays an oncogenic role in tumorigenesis of various types of cancers on the basis of the following findings 20) : (a) the wild-type WT1 gene was overexpressed in leukemia, 12) breast, 13,14) lung cancer, 15) and bone and soft-tissue sarcoma, 16) and HNSCC, 17) (b) high expression levels of WT1 mRNA significantly correlated with poor prognosis in leukemia 12) and breast cancer, 14) and with high tumor-stage in testicular germ-cell tumors 29) and HNSCC, 17) (c) growth of WT1-expressing cancer cells was inhibited by treatment with WT1 antisense oligomers, 10,18,19) (d) constitutive expression of WT1 blocked differentiation, and instead induced proliferation in response to granulocyte colonystimulating factor (G-CSF) in 32D cl3 myeloid progenitor cells 30) and normal myeloid progenitor cells. 31) The present study demonstrated that the WT1 gene was overexpressed in the majority of the primary colorectal adenocarcinomas examined and that the WT1 gene overexpressed in colorectal adenocarcinoma was the non-mutated, wild-type.…”

“…[1][2][3] The WT1 gene encodes a zinc finger transcription factor that regulates transcription of growth factor (PDGF-A chain, CSF-1, and IGF-II) [4][5][6] and growth factor receptor (IGF-IR) 7) genes and other genes (RAR-α, c-myc, and bcl-2). 8,9) We have demonstrated that the wild-type WT1 gene is expressed in cancer cells derived from various kinds of cancers, including colon cancer, 10,11) and overexpressed in primary leukemia, 12) breast, 13,14) lung cancer, 15) bone and soft-tissue sarcoma, 16) and head and neck squamous cell carcinoma (HNSCC). 17) Furthermore, growth of WT1-expressing cancer cells was inhibited by treatment with WT1 antisense oligomers.…”

Antiapoptotic function of 17AA(+)WT1 (Wilms' tumor gene) isoforms on the intrinsic apoptosis pathway

“…The WT1 gene encodes a protein with four zinc-fingers and is considered to be involved in transcriptional regulation of the genes such as PDGF-A chain (Gashler et al, 1992), CSF-1 (Harrington et al, 1993), IGF-II (Drummond et al, 1992), IGF-IR (Werner et al, 1993), and RAR-a (Goodyer et al, 1995) and in RNA metabolism (Larsson et al, 1995;Davies et al, 1998;Niksic et al, 2004). Although the WT1 gene has been considered as a tumor-suppressor gene, the wild-type WT1 gene is overexpressed in primary human leukemia (Inoue et al, 1994) and a wide variety of solid cancers, including lung (Oji et al, 2002), colon (Oji et al, 2003c), esophageal (Oji et al, 2004c), breast (Loeb et al, 2001;Miyoshi et al, 2002), thyroid (Oji et al, 2003b), pancreatic ductal cancer (Oji et al, 2004a), head and neck squamous cell carcinoma (HNSCC) (Oji et al, 2003a), astrocytic tumors (Oji et al, 2004b), and bone and soft-tissue sarcoma (Ueda et al, 2003). Moreover, the following findings indicated that the wild-type WT1 gene played oncogenic roles rather than tumor-suppressor functions in tumorigenesis of various types of cancers (Sugiyama, 2001): (a) high expression levels of WT1 mRNA correlated with poor prognosis in leukemia (Inoue et al, 1994) and breast cancer and with high tumor stage in testicular germ-cell tumors (Harada et al, 1999) and HNSCC (Oji et al, 2003a), (b) growth of WT1-expressing leukemia and solid cancer cells was inhibited by the treatment with WT1 antisense oligomers (Algar et al, 1996;Yamagami et al, 1996;Oji et al, 1999Oji et al, , 2004a, (c) block of differentiation but induction of proliferation by constitutive expression of 17AA( þ )KTS( þ )WT1 isoform in response to granulocyte colony-stimulating factor (G-CSF) in 32D cl3 myeloid progenitor (Inoue et al, 1998 ) and normal myeloid cells , (d) bone marrow ce...…”

Effective treatment of leukemic cell lines with wt1 siRNA

“…Exons 7-10 encode a member of the 'early growth response' family of Cys 2 -His 2 zinc finger transcription factors. 6 WT1 is overexpressed in various kinds of cancers like breast, 7,8 lung, 9 colon, 10 thyroid cancer, 11 bone and soft-tissue sarcoma 12 and pancreatic ductal adenocarcinoma. 13 The acute myelocytic leukemia (AML) is an acute myeloproliferative disease characterized by maturation arrest within the myeloid lineage.…”