Significance of maspin tumor suppressor genes in human tumors

• Project/Area Number: 16590290
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Human pathology
• Research Institution: Iwate medical University School of Medicine
• Principal Investigator: MAESAWA Chihaya Iwate Med.Univ., School of Med., Dept.of Pathol., Lecturer, 医学部, 助教授 (10326647)
• Co-Investigator(Kenkyū-buntansha): OGASAWARA Satoshi Iwate Med.Univ., School of Med., Dept.of Pathol., Research Associate, 医学部, 助手 (40326658)
• Project Period (FY): 2004 – 2005
• Project Status: Completed (Fiscal Year 2005)
• Budget Amount: ¥3,500,000 (Direct Cost: ¥3,500,000); Fiscal Year 2005: ¥800,000 (Direct Cost: ¥800,000); Fiscal Year 2004: ¥2,700,000 (Direct Cost: ¥2,700,000)
• Keywords: maspin / tumor suppressor genes / gastric cancer / hepatocellular carcinoma / biliary tract carcinomas / intestinal metaplasia / endometrioid adenocarcinoma / microarray / 癌抑止遺伝子 / 胃癌 / 肝癌 / 胆道癌 / リンパ節転移

Research Abstract

Cancer-associated DNA hypomethylation is as prevalent as cancer-linked hypermethylation, but the biological significance of DNA hypomethylation in carcinogenesis is less understood. The expression of maspin (mammary serpin) in cancerous and non-cancerous tissues. Paradoxical maspin expression due to epigenetic modification has been addressed in several cancer cell types. To elucidate the role of the maspin gene in thyroid cancer, we studied methylation status in the promoter region and its expression in human cancers. Their methylation status evaluated by the methylation-specific PCR method showed a good inverse correlation with their immunoreactivity in surgically resected specimens. Our data suggest that over-expression of Maspin by DNA hypomethylation is closely associated with morphological dedifferentiation in thyroid cancers. Immunoreactivity for maspin was observed in metaplastic (intestinal metaplasia) and cancerous tissues. There aberrant expression were caused by the disruption of the epigenetic status at the promoter region. Aberrant maspin expression appears to be closely associated with morphological changes such as metaplasia, dysplasia and dedifferentiation, probably as a result of disruption of epigenetic expression mechanisms.

Research Products

• [Journal Article] Aberrant maspin expression in gallbladder epithelium is associated with intestinal metaplasia in patients with cholelithiasis. (2006)
  • Author(s): Maesawa C, Ogasawara S, Yashima-Abo A, Kimura T, Kotani K, Masuda S, Nagata Y, Iwaya T, Suzuki K, Oyake T, Akiyama Y, Kawamura H, Masuda T
  • Journal Title: J Clin Pathol. 59(3) Pages: 328-330
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Aberrant maspin expression in human endometrial cancer. (2006)
  • Author(s): Murai S, Maesawa C, Sugiyama T, Masuda T
  • Journal Title: Cancer Sci (in press.)
  • NAID: 10018767453
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Aberrant maspin expression in gallbladder epithelum is associated with intestinal metaplasia in patients with cholelithiasis. (2006)
  • Author(s): Maesawa C
  • Journal Title: J Clin Pathol 59(3) Pages: 328-330
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Aberrant maspin expression in human endometrial cancer s (2006)
  • Author(s): Murai S, Maesawa C, Masuda T, Sugiyama T
  • Journal Title: Cancer Sci (In press)
• [Journal Article] Activated toll-like receptor 4 in monocytes is associated with heart failure after acute myocardial infarction (2006)
  • Author(s): Satoh M, Shimoda Y, Maesawa C, Akatsu T, Ishikawa Y, Minami Y, Hiramori K, Nakamura M.
  • Journal Title: Int J Cardiol.2005 Jul 25; (In press)(Epub ahead of print)
• [Journal Article] Mutations of the epidermal growth factor receptor gene in gastrointestinal fract tumor cell lines (2006)
  • Author(s): Kimura T, Maesawa C, Ikeda K, Wakabayashi G, Masuda T
  • Journal Title: Oncol Rep (In press)
• [Journal Article] Interferon-gamma down-regulates expression of tumor necrosis factor-alpha converting enzyme/a disintegrin and metalloproteinase 17 in activated hepatic stellate cells of rats. (2006)
  • Author(s): Fujita T, Maesawa C, Oikawa K, Nitta H, Wakabayashi G, Masuda T
  • Journal Title: Int J Mol Med 17(4) Pages: 605-616
• [Journal Article] Aberrant maspin expression in gallbladder epithelium is associated with intestinal metaplasia in patients with cholelithiasis. (2006)
  • Author(s): Maesawa C, Ogasawara S, Yashima-Abo A, Kimura T, Kotani K, Masuda S, Nagata Y, Iwaya T, Suzuki K, Oyake T, Akiyama Y, Kawamura H, Masuda T.
  • Journal Title: J Clin Pathol 59(3) Pages: 328-330
• [Journal Article] Epigenetic status and aberrant expression of the maspin gene in human hepato-biliarv tract carcinomas. (2005)
  • Author(s): Fujisawa K, Maesawa C, Sato R, Wade K, Ogasawara S, Akiyama Y, Takeda M, Fujita T, Otsuka K, Higuchi T, Suzuki K, Saito K, Masuda T
  • Journal Title: Lab Invest 85(2) Pages: 214-24
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Consensus JH gene probes with conjugated 3'-minor groove binder for monitoring minimal residual disease in acute lymphoblastic leukemia. (2005)
  • Author(s): Uchiyama M, Maesawa C, Yashima-Abo A, Tarusawa M, Endo M, Sugawara W, Chida S, Onodera S, Tsukushi Y, Ishida Y, Tsuchiya S, Masuda T
  • Journal Title: J Mol Diagn 7(1) Pages: 121-126
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Infrequent mutation of the human envoplakin gene is closely linked to the tylosis oesophageal cancer locus in sporadic oesophageal squamous cell carcinomas. (2005)
  • Author(s): Iwaya T, Maesawa C, Kimura T, Ogasawara S, Ikeda K, Kimura Y, Noda Y, Ishida K, Sato N, Saito K, Masuda T
  • Journal Title: Oncol Rep 13(4) Pages: 703-707
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Expression of human telomerase reverse transcriptase splice variants is well correlated with low telomerase activity in osteosarcoma cell lines. (2005)
  • Author(s): Fujiwara-Akita H, Maesawa C, Honda T, Kobayashi S, Masuda T
  • Journal Title: Int J Oncol 26(4) Pages: 1009-1016
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Distinguishing between proliferating nodal lymphoid blasts in chronic myelogenous leukemia and non-Hodgkin lymphoma : report of three cases and detection of a bcr/abl fusion signal by single-cell analysis. (2005)
  • Author(s): Yashima-Abo A, Satoh T, Abo T, Aoki Y, Kowata.S, Ito S, Ishida Y, Fujiwara H, Maesawa C, Masuda T
  • Journal Title: Pathol Int 55(5) Pages: 273-9
  • NAID: 10016475387
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Liver cirrhosis induced by long-term administration of a daily low dose of amiodarone : a case report.. (2005)
  • Author(s): Oikawa H, Maesawa C, Sato R, Oikawa K, Yamada H, Oriso S, Ono S, Yashima-Abo A, Kotani K, Suzuki K, Masuda T
  • Journal Title: World J Gastroenterol. 11(34) Pages: 5394-5397
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Epigenetic status and aberrant expression of the maspin gene in human hepato-biliary tract carcinomas. (2005)
  • Author(s): Fujisawa K
  • Journal Title: Lab Invest 85(2) Pages: 214-224
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Consensus JH gene probes with conjugated 3'-minor groove binder for monitoring minimal residual disease in acute lymphoblastic leukemia. (2005)
  • Author(s): Uchiyama M
  • Journal Title: J Mol Diagn 7(1) Pages: 121-126
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Infrequent mutation of the human envoplakin gene is closely linked to the tylosis oesophageal cancer locus in sporadic oesophageal squamous cell carcinomas. (2005)
  • Author(s): Iwaya T
  • Journal Title: Oncol Rep 13(4) Pages: 703-707
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Expression of human telomerase reverse transcriptase splice variants is well correlated with low telomerase activity in osteosarcoma cell lines. (2005)
  • Author(s): Fujiwara-Akita H
  • Journal Title: Int J Oncol 26(4) Pages: 1009-1016
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Distinguishing between proliferating nodal lymphoid blasts in chronic myelogenous leukemia and non-Hodgkin lymphoma : report of three cases and detection of a bcr/abl fusion signal by single-cell analysis. (2005)
  • Author(s): Yashima-Abo A
  • Journal Title: Pathol Int 55(5) Pages: 273-279
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Liver cirrhosis induced by long-term administration of a daily low dose of amiodorone : a case report. (2005)
  • Author(s): Oikawa H
  • Journal Title: World J Gastroenterol 11(34) Pages: 5394-5397
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Infrequent mutation of the human envoplakin gene is closely linked to the tylosis oesophageal cancer locus in sporadic oesophageal squamous cell carcinomas. (2005)
  • Author(s): Iwaya T, Maesawa C, Kimura T, Ogasawara S, Ikeda K, Kimura Y, Noda Y, Ishida K, Sato N, Saito K, Masuda T.
  • Journal Title: Oncol Rep 13(4) Pages: 703-707
• [Journal Article] Epigenetic status and aberrant expression of the maspin gene in human hepato-biliary tract carcinomas. (2005)
  • Author(s): Fujisawa K, Maesawa C, Sato R, Wada K, Ogasawara S, Akiyama Y, Takeda M, Fujta T, Otsuka K, Higuchi T, Suzuki K, Saito K, Masuda T.
  • Journal Title: Lab Invest 85・2 Pages: 214-222
• [Journal Article] Gene expression profiles in human gastric cancer : expression of maspin correlates with lymph node metastasis. (2005)
  • Author(s): Terashima M, Maesawa C, Oyama K, Ohtani S, Akiyama Y, Ogasawara S, Takagane A, Saito K, Masuda T, Kanzaki N, Matsuyama S, Hoshino Y, Kogure M, Gotoh M, Shirane M, Mori M.
  • Journal Title: Br J Cancer (印刷中)
• [Journal Article] Human PinX1, a potent telomerase inhibitor, is not involved in human gastrointestinal tract carcinoma. (2004)
  • Author(s): Akiyama Y, Maesawa C, Wada K, Fujisawa K, Itabashi T, Noda Y, Honda T, Sato N, Ishida K, Takagane A, Saito K, Masuda T
  • Journal Title: Oncol Rep. 11(4) Pages: 871-487
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Acute renal failure due to leukemic cell infiltration followed by relapse at multiple extramedullary sites in a child with acute lymphoblastic leukemia. (2004)
  • Author(s): Sato A, Imaizumi M, Chikaoka S, Niizuma H, Hoshi Y, Takeyama J, Fujii K, Nishio T, Watanabe M, Maesawa C, Hayashi Y, Iinuma K
  • Journal Title: Leuk Lymphoma :. 45(4) Pages: 825-8
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Prognostic significance of peritoneal minimal residual disease in gastric cancer detected by reverse transcription-polymerase chain reaction. (2004)
  • Author(s): Oyama K, Terashima M, Takagane A, Maesawa C
  • Journal Title: Br J Surg 91(4) Pages: 435-443
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Aberrant expression of the maspin gene associated with epigenetic modification in melanoma cells. (2004)
  • Author(s): Wada K, Maesawa C, Akasaka T, Masuda T
  • Journal Title: J Invest Dermatol 122(3) Pages: 805-811
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Prevention of critical telomere shortening by oestradiol in human normal hepatic cultured cells and carbon tetrachloride induced rat liver fibrosis. (2004)
  • Author(s): Sato R, Maesawa C, Fujisawa K, Wade K, Oikawa K, Takikawa Y, Suzuki K, Oikawa H, Ishikawa K, Masuda T
  • Journal Title: Gut 53(7) Pages: 1001-1009
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Biacore's SPR technology for the development of telomere/telomerase-targeted theranips. (2004)
  • Author(s): Maesawa C, Oikawa K, Fujiwara-Akita H, Masuda T
  • Journal Title: BIACORE JOURNAL 4(1) Pages: 7-9
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Short consensus probes with 3'-minor groove binder of the immunoglobulin heavy-chain gene for real-time quantitative PCR in B-cell non-Hodgkin lymphomas. (2004)
  • Author(s): Uchiyama M, Maesawa C, Yashima-Abo A, Tarusawa M, Satoh M, Satoh T, Ishida Y, Ito S, Murai K, Enomoto S, Utsugisawa T, Masuda T
  • Journal Title: Lab Invest 84(7) Pages: 932-936
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] PinX1, a potent telomerase inhibitor, is not involved in human gastrointestinal tract carcinoma. (2004)
  • Author(s): Akiyama Y
  • Journal Title: Oncol Rep 11(4) Pages: 871-874
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Acute renal failure due to leukemic cell infiltration followed by relapse at multiple extramedullary sites in a child with acute lymphoblastic leukemia. (2004)
  • Author(s): Sato A
  • Journal Title: Leuk Lymphoma 45(4) Pages: 825-828
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Prognostic significance of peritoneal minimal residual disease in gastric cancer detected by reverse transcription-polymerase chain reaction. (2004)
  • Author(s): Oyama K
  • Journal Title: Br J Surg 91(4) Pages: 435-443
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Aberrant expression of the maspin gene associated with epigenetic modification in melanoma cells. (2004)
  • Author(s): Wada K
  • Journal Title: J Invest Dermatol 122(3) Pages: 805-811
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Prevention of critical telomere shortening by oestradiol in human normal hepatic cultured cells and carbon tetrachloride induced rat liver fibrosis (2004)
  • Author(s): Sato R
  • Journal Title: Gut 53(7) Pages: 1001-1009
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Biacore's SPR technology for the development of telomere/telomerase-targeted therapies (2004)
  • Author(s): Maesawa C
  • Journal Title: BIACORE JOURNAL 4(1) Pages: 7-9
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Short consensus probes with 3'-minor groove binder of the immunoglobulin heavy-chain gene for real-time quantitative PCR in B-cell non-Hodgkin lymphomas. (2004)
  • Author(s): Uchiyama M
  • Journal Title: Lab Invest 84(7) Pages: 932-936
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Aberrant maspin expression inhuman endometrial cancer.
  • Author(s): Murai S
  • Journal Title: Cancer Sci (in press)
  • Description: 「研究成果報告書概要(欧文)」より