Overexpression of the Wilms' tumor gene <i>WT1</i> in colorectal adenocarcinoma

Oji, Yusuke; Yamamoto, Hirofumi; Nomura, Motonari; Nakano, Yoko; Ikeba, Ai; Nakatsuka, Shin‐ichi; Abeno, Sakie; Kiyotoh, Eiji; Jomgeow, Tanyarat; Sekimoto, Mitsugu; Nezu, Riichiro; Yoshikawa, Yukinobu; Inoue, Yasuhiro; Hosen, Naoki; Kawakami, Manabu; Tsuboi, Akihiro; Oka, Y.; Ogawa, Hiroyasu; Souda, Shigeo; Aozasa, Katsuyuki; Monden, Morito; Sugiyama, Haruo

doi:10.1111/j.1349-7006.2003.tb01507.x

Cited by 108 publications

(90 citation statements)

References 35 publications

(42 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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.…”

Section: Discussionmentioning

confidence: 97%

“…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.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Immunohistochemical detection of WT1 protein in a variety of cancer cells

et al. 2006

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 97%

mentioning

confidence: 99%

Immunohistochemical detection of WT1 protein in a variety of cancer cells

et al. 2006

Self Cite

View full text Add to dashboard Cite

show abstract

“…This mouse represents a useful tool for leukemia research as well as other types of malignancies, since WT1 is overexpressed in many different types of cancer. 33,34 In addition, the GFP-reporter system will aid studies to understand the role of WT1 in normal development of kidney, 22 genital system 35 or other tissues 36,37 in which WT1 has an important role. Although Hastie and colleagues 38 previously generated WT1-LacZ reporter transgenic mice, a 40 consistent with the lack of its expression on HSCs.…”

Section: Discussionmentioning

confidence: 99%

The Wilms’ tumor gene WT1-GFP knock-in mouse reveals the dynamic regulation of WT1 expression in normal and leukemic hematopoiesis

et al. 2007

View full text Add to dashboard Cite

The Wilms' tumor gene WT1 is overexpressed in most of human leukemias regardless of disease subtypes. To characterize the expression pattern of WT1 during normal and neoplastic hematopoiesis, we generated a knock-in reporter green fluorescent protein (GFP) mouse (WT1 GFP/ þ ) and assayed for WT1 expression in normal and leukemic hematopoietic cells. In normal hematopoietic cells, WT1 was expressed in none of the long-term (LT) hematopoietic stem cells (HSC) and very few (o1%) of the multipotent progenitor cells. In contrast, in murine leukemias induced by acute myeloid leukemia 1 (AML1)/ ETO þ TEL/PDGFbR or BCR/ABL, WT1 was expressed in 40.5 or 38.9% of immature c-kit þ lin À Sca-1 þ (KLS) cells, which contained a subset, but not all, of transplantable leukemic stem cells (LSCs). WT1 expression was minimal in normal fetal liver HSCs and mobilized HSCs, both of which are stimulated for proliferation. In addition, overexpression of WT1 in HSCs did not result in proliferation or expansion of HSCs and their progeny in vivo. Thus, the mechanism by which expansion of WT1-expressing cells occurs in leukemia remains unclear. Nevertheless, our results demonstrate that the WT1 GFP/ þ mouse is a powerful tool for analyzing WT1-expressing cells, and they highlight the potential of WT1, as a specific therapeutic target that is expressed in LSCs but not in normal HSCs.

show abstract

“…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...…”

Section: Introductionmentioning

confidence: 99%