Molecular basis of the atypism of neoplastic cells-Participation of mutations and downregulation of FXYD3-

2010 Fiscal Year Final Research Report

• Project/Area Number: 21790325
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Pathological medical chemistry
• Research Institution: Yokohama City University
• Principal Investigator: OKUDELA Koji Yokohama City University, 医学部, 助教 (10326027)
• Project Period (FY): 2009 – 2010
• Keywords: 異型性 / FXYD3 / 肺癌 / KRAS

Research Abstract

Our preliminary study revealed that FXYD3 expression was downregulated in oncogenic KRAS-transduced airway epithelial cells. This result interested us to investigate the role of FXYD3 in carcinogenesis of the lung. FXYD3 mRNA and protein levels were lower in most of the lung cancer cell lines than in either the non-cancerous lung tissue or airway epithelial cells. Its protein levels were lower in a considerable proportion of primary lung cancers than in non-tumoral airway epithelia. The levels reduced in parallel with the dedifferentiation process. Also, a somatic point mutation, g55c (D19H), was found in one cell line. Forced expression of the wild-type FXYD3, but not the mutant, restored the well-demarcated distribution of cortical actin in cancer cells that had lost FXYD3 expression, suggesting FXYD3 to play roles in the maintenance of cytoskeletal integrity. No association between its expression and the promoter's methylation status was observed. Inactivation of FXYD3 through a gene mutation or unknown mechanism could be one causes of the atypical shapes of cancer cells and play a potential role in the progression of lung cancer.

Research Products

• [Journal Article] KRAS gene mutations in lung cancer : particulars established and issues unresolved. (2010)
  • Author(s): Okudela K, Woo T, Kitamura H.
  • Journal Title: Pathol Int. 60(10) Pages: 651-660
• [Journal Article] Insulin-like growth factor binding protein-4 gene silencing in lung adenocarcinomas. (2010)
  • Author(s): Sato H, Sakaeda M, Ishii J, Kashiwagi K, Shimoyamada H, Okudela-K, Kitamura H, Yazawa T al.
  • Journal Title: Pathol Int. in press.
• [Journal Article] Early growth response-1 induces and enhances vascular endothelial growth factor-a expression in lung cancer cells. (2010)
  • Author(s): Shimoyamada H, Yazawa T, Sato H, Okudela K, Ishii J, Sakaeda M, Kashiwagi K, Suzuki T, Mitsui H, Woo T, Tajiri M, Ohmori T, Ogura T, Masuda M, Oshiro H, Kitamura H.
  • Journal Title: Am J Pathol. 177(1) Pages: 70-83
• [Journal Article] Proposal of an Altered Histological Sub-typing System for Lung Adenocarcinoma . significant prognostic values for stage I disease. (2010)
  • Author(s): Okudela K, Woo T, Mitsui T, Yazawa T, Shimoyamada H, Tajiri H, Oagawa N, Masuda M, Katamura H.
  • Journal Title: Int J Clin Exp Pathol 3 Pages: 348-366
• [Journal Article] A case of epithelial-myoepithelial carcinoma of the bronchus - A review of reported cases and a comparison with other salivary gland-type carcinomas of the bronchus. (2010)
  • Author(s): Okudela K, Yazawa T, Tajiri M, Omori T, Takahashi K, Woo T, Shimoyamada H, Ogawa N, Kitamura H.
  • Journal Title: Pathol Res Pract 206 Pages: 101-107
• [Journal Article] A case of malignan fibrous histiocytoma of the thymus. (2010)
  • Author(s): Samejima M, Tajiri M, Takahashi K, Omori T, Okudela K, et al.
  • Journal Title: Ann Thoracic Oncology 89 Pages: 2003-2005
• [Journal Article] Morphometric Profiling of Lung Cancers-its association with clinicopathologic, biological and molecular genetic features-. (2010)
  • Author(s): Okudela K, Woo T, Mitsui T, Yazawa T, Shimoyamada H, Tajiri H, Oagawa N, Masuda M, Katamura H.
  • Journal Title: Am J Surg Pathol 34 Pages: 243-255
• [Journal Article] Secreted form of EphA7 in lung cancer. (2010)
  • Author(s): Tsuboi M, Mori H, Bunai T, Kageyama S, Suzuki M, Okudela K, Takamochi K, Ogawa H, Niwa H, Shinmura K, Sugimura H.
  • Journal Title: Int J Oncology 36 Pages: 635-640
• [Journal Article] Down-regulation of FXYD3 expression in human lung cancers : its mechanism and potential role in carcinogenesis. (2009)
  • Author(s): Okudela K, Yazawa T, Ishii J, Woo T, Mitsui H, Bunai T, Sakaeda M, Shimoyamada H, Sato H, Tajiri M, Ogawa N, Masuda M, Sugimura H, Kitamura H.
  • Journal Title: Am J Pathol 175 Pages: 2646-2656
• [Journal Article] Down-regulation of DUSP6 expression in lung cancer : its mechanism and potential role in carcinogenesis. (2009)
  • Author(s): Okudela K, Yazawa T, Woo T, Sakaeda M, Ishii J, Mitsui H, Shimoyamada H, Sato H, Tajiri M, Ogawa N, Masuda M, Takahashi T, Sugimura H, Kitamura H.
  • Journal Title: Am J Pathol 175 Pages: 867-881
• [Journal Article] Role of 3'Phosphoinositides in Oncogenic KRAS-Induced Modulation of Shape and Motility of Airway Epithelial cells. (2009)
  • Author(s): Okudela K, Yazawa T, Suzuki T, Sugimura H, Kitamura H
  • Journal Title: Pathol Int 59 Pages: 28-37
• [Journal Article] Significant association between EGFR-mutated lung adenocarcinoma and past illness from gastric cancer or uterine myoma : its implication in carcinogenesis. (2009)
  • Author(s): Okudela K, Woo T, Yazawa T, Ogawa N, Tajiri M, Masuda M, Kitamura H.
  • Journal Title: Lung Cancer 66 Pages: 287-291
• [Journal Article] Prognostic value of KRAS mutations and Ki-67 expression in stage I lung adenocarcinomas. (2009)
  • Author(s): Woo T, Okudela K, Yazawa T, Wada N, Ogawa N, Ishiwa N, Tajiri M, Rino Y, Kitamura H, Masuda M.
  • Journal Title: Lung Cancer 65 Pages: 355-362
• [Journal Article] Cancer stem cell : implications in cancer biology and therapy with special reference to lung cancer. (2009)
  • Author(s): Kitamura H, Okudela K, Yazawa T, Sato H, Shimoyamada H.
  • Journal Title: Lung Cancer 66 Pages: 275-281
• [Journal Article] Small cell lung cancer : significance of RB alterations and TTF-1 expression in its carcinogenesis, phenotype, and biology. (2009)
  • Author(s): Kitamura H, Yazawa T, Sato H, Okudela K, Shimoyamada H.
  • Journal Title: Endocr Pathol 20 Pages: 101-107
• [Journal Article] Neuroendocrine cancer-specific up-regulating mechanism of insulin-like growth factor binding protein-2 in small cell lung cancer. (2009)
  • Author(s): Yazawa T, Sato H, Shimoyamada H, Okudela K, Woo T, Tajiri M, Ogura T, Ogawa N, Suzuki T, Mitsui H, Ishii J, Miyata C, Sakaeda M, Goto K, Kashiwagi K, Masuda M, Takahashi T, Kitamura H.
  • Journal Title: Am J Pathol 175 Pages: 976-987
• [Presentation] Proposal of an Altered Histological Sub-typing System for Lung Adenocarcinoma. (2010)
  • Author(s): 奥寺康司, 他
  • Organizer: 日本病理学会総会(99回).
  • Place of Presentation: 東京
  • Year and Date: 2010-04-27
• [Presentation] 異型性の分子基盤(イオンチャンネル制御因子FXYD3 の関与). (2009)
  • Author(s): 奥寺康司, 他
  • Organizer: 日本病理学会総会(98回).
  • Place of Presentation: 石川
  • Year and Date: 2009-05-02
• [Book] Cancer Stem Cell in Lung Cancer. (2010)
  • Author(s): Okudela K, Katayam A, Nagahra N, Kitamura H.
  • Publisher: Nova Science Publication