Overexpression of the Wilms' tumor gene WT1 in pancreatic ductal adenocarcinoma

Cancer Science - Tập 95 Số 7 - Trang 583-587 - 2004
Yusuke Oji1, Shoji Nakamori2, Masahiro Fujikawa3, Shin‐ichi Nakatsuka4, Asumi Yokota1, N Tatsumi1, Sakie Abeno1, Ai Ikeba1, S Takashima1, Masanori Tsujie2, Hirofumi Yamamoto2, Masato Sakon2, Riichiro Nezu3, Kiyoshi Kawano5, Sumiyuki Nishida6, Kazuhiro Ikegame7, Manabu Kawakami7, Akihiro Tsuboi7, Yoshihiro Oka6, Kiyoshi Yoshikawa3, Katsuyuki Aozasa4, Morito Monden2, Haruo Sugiyama1
1Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, 1-7 Yamada-Oka, Suita, Osaka 565-0871
2Department of Surgery and Clinical Oncology, Osaka University Graduate School of Medicine, 2-2 Yamada-Oka, Suita, Osaka 565-0871
3Department of Surgery, Osaka Rosai Hospital, 1179-3 Nagasone-cho, Sakai, Osaka 591-8025
4Department of Pathology, Osaka University Graduate School of Medicine, 2-2 Yamada-Oka, Suita, Osaka 565-0871
5Department of Pathology, Osaka Rosai Hospital, 1179-3 Nagasone-cho, Sakai, Osaka 591-8025
6Department of Molecular Medicine, Osaka University Graduate School of Medicine, 2-2 Yamada-Oka, Suita, Osaka 565-0871
7Department of Cancer Immunotherapy, Osaka University Graduate School of Medicine, 2-2 Yamada-Oka, Suita, Osaka 565-0871

Tóm tắt

The expression of the Wilms' tumor gene WT1 was examined by immunohistochemistry in 40 cases of pancreatic ductal adenocarcinoma. WT1 protein was expressed in 30 (75%) of the 40 pancreatic ductal adenocarcinomas, but not in the remaining 10 (25%). In normal pancreatic ductal cells, WT1 protein was undetectable. No correlations between WT1 expression and clinicopathological parameters such as age, sex, T or N stage, tumor location, and tumor differentiation were observed. Treatment with WT1 anti‐sense oligomers significantly inhibited the growth of five human pancreatic cancer cell lines, PSN1, MiaPaCa2, ASPC1, BxPC3, and PCI6, expressing the WT1 gene. These results indicate an important role of the WT1 gene in the tumorigenesis of pancreatic ductal adenocarcinoma expressing WT1 and provide a rationale for new treatment strategies to treat pancreatic ductal adenocarcinoma by targeting the WT1 gene and its product.

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Tài liệu tham khảo

10.1016/0092-8674(90)90601-A

10.1038/343774a0

10.1038/353431a0

10.1073/pnas.89.22.10984

10.1016/S0021-9258(19)36920-0

10.1126/science.1323141

10.1073/pnas.90.12.5828

Goodyer P, 1995, Repression of the retinoic acid receptor‐alpha gene by the Wilms' tumor suppressor gene product, wtl, Oncogene, 10, 1125

Hewitt SM, 1995, Regulation of the proto‐oncogenes bcl‐2 and c‐myc by the Wilms' tumor suppressor gene WT1, Cancer Res, 55, 5386

Miwa H, 1992, Expression of the Wilms' tumor gene (WT1) in human leukemias, Leukemia, 6, 405

10.1111/j.1349-7006.1999.tb00733.x

10.1007/s004320050037

10.1182/blood.V84.9.3071.3071

Loeb DM, 2001, Wilms' tumor suppressor gene (WT1) is expressed in primary breast tumors despite tumor‐specific promoter methylation, Cancer Res, 61, 921

Miyoshi Y, 2002, High expression of Wilms' tumor suppressor gene predicts poor prognosis in breast cancer patients, Clin Cancer Res, 8, 1167

10.1002/ijc.10476

10.1111/j.1349-7006.2003.tb01507.x

10.1111/j.1349-7006.2003.tb01490.x

10.1111/j.1349-7006.2003.tb01477.x

10.1111/j.1349-7006.2003.tb01432.x

10.1182/blood.V87.7.2878.bloodjournal8772878

Algar EM, 1996, A WT1 antisense oligonucleotide inhibits proliferation and induces apoptosis in myeloid leukaemia cell lines, Oncogene, 12, 1005

10.1007/BF02981935

Hruban RH, 1993, K‐ras oncogene activation in adenocarcinoma of the human pancreas. A study of 82 carcinomas using a combination of mutant‐enriched polymerase chain reaction analysis and allele‐specific oligonucleotide hybridization, Am J Pathol, 143, 545

10.1016/S0046-8177(96)90364-0

Wilentz RE, 1998, Inactivation of the p16 (INK4A) tumor‐suppressor gene in pancreatic duct lesions: loss of intranuclear expression, Cancer Res, 58, 4740

Harada Y, 1999, WT1 gene expression in human testicular germ cell tumors, Mol Urol, 3, 357

10.1182/blood.V91.8.2969.2969_2969_2976

10.1016/S0145-2126(99)00037-5

10.1007/BF02986614

10.1093/hmg/ddh040

10.4049/jimmunol.164.4.1873

10.1182/blood.V95.7.2198

10.1007/BF02982574

10.2174/1568009023334088

10.1007/s002510050018

10.1182/blood.V95.1.286

Makita M, 2002, Antilung cancer effect of WT1‐specific cytotoxic T lymphocytes, Clin Cancer Res, 8, 2626

10.1007/BF02983241

10.1111/j.1348-0421.2004.tb03503.x