Analysis of lung carcinogenesis by hnRNP B1, a RNA binding protein, using SPC-hnRNP B1 transgenic mouse models

• Project/Area Number: 14570555
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Saga University
• Principal Investigator: SUEOKA Eizaburo Saga University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (00270603)
• Co-Investigator(Kenkyū-buntansha): SUEOKA Naoko Saga University, Faculty of Medicine, Assistant Professor, 医学部, 講師 (20321846)
• Project Period (FY): 2002 – 2003
• Project Status: Completed (Fiscal Year 2003)
• Budget Amount: ¥3,500,000 (Direct Cost: ¥3,500,000); Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000); Fiscal Year 2002: ¥2,200,000 (Direct Cost: ¥2,200,000)
• Keywords: Lung Cancer / RNA biniding protein / hnRNP B1 / transgenic mouse / surfactant Protein C / 肺癌

Research Abstract

We identified that hnRNP B1, a splicing variant of hnRNP A2, was overexpressed in nuclei of human lung cancer cells, from the early stage to the advanced : Moreover, hnRNP B 1 was overexpressed in squamous cell carcinoma in various organs, such as oral cavity and esophagus, in addition to lung. To clarify the role of hnRNP B1 for lung carcinogenesis, we constructed the chimeric genes fused with surfactant protein C promoter and hnRNP B1 cDNA. We obtained several transgenic clones of SPC-hnRNP BI, hnRNP A2 and GFP after introduction into ES cell neclei. Heterogenic transgenic mice were back-crossed to parental wild mice and we obtained F3 generations and homogygous mouse clones. High expression levels of hnRNP B1 protein were confirmed in the lungs of homogygous mice by immunohistocherriistry. Recent our study found hnRNP B1 interacted with a DNA repair protein complex and regulated its activity. To determine the precise role of hnRNP B1 in lung carcinogenesis associated with alteration of DNA repair activity, sequential analysis of pathological and cytogenetical analyses were under investigation.

Research Products

• [Publications] Fujimoto N, Sueoka N, Sueoka E, Okabe S, et al.: "Lung cacner prevention with (-)-epigallocatechin gallate using monitoring by heterogeneous nuclear ribonucleoprotein B1."Int.J.Oncol.. 20. 1233-1239 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Tominaga M, Sueoka N, Irie K, Iwanaga K, Sueoka E et al.: "Detection and discrimination of preneoplastic and early stages of lung adenocarcinoma using hnRNP B1 combined with the cell cycle-related markers p16, cyclin D1, and Ki-67."Lung Cancer. 40. 45-53 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Wu S, Sato M, Endo C, Sakurada A, Dong B, et al.: "hnRNP B1 protein may be a possible prognostic factor in squamous cell carcinoma of the lung."Lung Cancer. 40. 179-186 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Iwanaga K, Sueoka N, Akemi S, Sakuragi T: "Alteration of expression or phosphorylation status of tob, a novel tumor suppressor gene product, is an early event in lung cancer"Cancer Letters. 202. 71-79 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Fujimoto N, Sueoka N, Sueoka E, Okabe S, Suganuma M, Harada M, Fujiki H.: "Lung cacner prevention with (-)-epigallocatechin gallate using monitoring by heterogeneous nuclear ribonucleoi rotein B1."Int.J.Oncol.. 20. 1233-1239 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Tominaga M, Sueoka N, Irie K, Iwanaga K, Tokunaga O, Hayashi S, Nakachi K, Sueoka E.: "Detection and discrimination of preneoplastic and early stages of lung adenocarcinoma using hnRNP B1 combined with the cell cycle-related markers p16, cyclin Dl, and Ki-67."Lung Cancer. 40. 45-53 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Wu S, Sato M, Endo C, Sakurada A, Dong B, Aikawa H, Chen Y, Okada Y, Matsumura, Y.Sueoka E, Kondo T.: "hnRNP B1 pirotein may be a possible prognostic factor in squamous cell carcinoma of the lung."Lung Cancer. 41. 179-186 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Iwanaga K, Sueoka N, Akemi S, Sakuragi T, Sakao Y, Tominaga M, Suzuki T, Yoshida Y, K-Tsuzuku J, Yamamoto T, Hayashi S, Nagasawa K, Sueoka E.: "Alteration of expression or phosphorylation status of tob, a novel tumor suppressor gene product, is an early event in "lung cancer,"Cancer Letters. 202. 71-79 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Tominaga, M.: "Detection and discrimination of preneoplastic and early stages of lung adenocarcinoma using hnRNP B1 combined with the cell cycle-related markers p16, cyclin D1, and Ki-67"Lung Cancer. 40. 45-53 (2003)
• [Publications] Iwanaga K: "Alteration of expression or phosphorylation status of tob, a novel tumor suppress or gene product, is an early event in lung cancer."Cancer Letter. 202. 71-79 (2003)
• [Publications] Wu S: "hnRNP B1 protein may be a possible prognostic factor in squamous cell carcinoma of the lung"Lung Cancer. 41. 179-186 (2003)
• [Publications] Tominaga M, Sueoka N, Irie K, et al.: "Detection and discrimination of preneoplastic and early stages of lung adenocarcinoma using hnRNP B1 combined with the cell cycle-related markers p16, cyclin D1, and Ki-67"Lung Cancer. (in press). (2003)