Understanding the molecular mechanisms of breast cancer by targeting mutant BRCA1 in hereditary breast cancer cells

• Project/Area Number: 22700888
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Tumor biology
• Research Institution: Aichi Medical University
• Principal Investigator: SIVASUNDARAM Karnan 愛知医科大学, 医学部, 助教 (30557096)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: がん制御遺伝子 / ヒト細胞遺伝子改変法 / BRCA1 / ヒト細胞遺伝子改変

Research Abstract

In this study, we sought to generate experimental platforms that help to understand the mechanism of how a mutation of BRCA1 tumor suppressor gene leads to the onset of human hereditary breast cancer. To this end, we used the technology of human somatic cell gene targeting in an attempt to perform the targeted correction of BRCA1 mutations in 2 cell lines derived from human hereditary breast cancers harboring homozygous BRCA1 mutations, as well as the targeted knock-in of 2 missense mutations into an immortalized human breast epithelial cell line MCF-10A which carries wild-type BRCA1.

Research Products

• [Journal Article] Mutation of a single allele of the cancer susceptibility gene BRCA1 leads to genomic instability in human breast epithelial cells. (2011)
  • Author(s): Konishi H, Mohseni M, Tamaki A, Garay JP, Croessmann S, Karnan S, Ota A, Wong HY, Konishi Y, Karakas B, Tahir K, Abukhdeir AM, Gustin JP, Cidado J, Wang GM, Cosgrove D, Cochran R, Jelovac D, Higgins MJ, Arena S, Hawkins L, Lauring J, Gross AL, Heaphy CM, Hosokawa Y, Gabrielson E, Meeker AK, Visvanathan K, Argani P, Bachman KE, Park BH.
  • Journal Title: Proc Natl Acad Sci U S A Volume: 108 Issue: 43 Pages: 17773-8
  • DOI: 10.1073/pnas.1110969108
  • Peer Reviewed
• [Journal Article] Genomic profiling combined with gene expression profiling in primary central nervous system lymphoma (2011)
  • Author(s): Sung CO, Kim SC, Karnan S, Karube K, Shin HJ, Nam DH, Suh YL, Kim SH, Kim JY, Kim SJ, Kim WS, Seto M, Ko YH
  • Journal Title: Blood Volume: 117 Issue: 4 Pages: 1291-300
  • DOI: 10.1182/blood-2010-07-297861
  • Peer Reviewed
• [Journal Article] Establishment of an adult T-cell leukemia cell line(HU-ATTAK) dependent for proliferation on human umbilical cord vein endothelial cells (2011)
  • Author(s): Kagami Y, Karnan S, Nakagawa A, Oshiro K, Kato H, Koike K, Morishima Y, Seto M
  • Journal Title: The Open Leukemia Journal Volume: 4 Issue: 1 Pages: 1-8
  • DOI: 10.2174/1876816401104010001
  • Peer Reviewed
• [Journal Article] Genomic profiling combined with gene expression profiling in primary central nervous system lymphoma (2011)
  • Author(s): Sung CO
  • Journal Title: Blood Volume: 117巻 Pages: 1291-1300
  • Peer Reviewed
• [Journal Article] FIL-4/CD40L co-stimulation induces long-term proliferation for CD10-positive germinal center B cell-like diffuse large B-cell lymphomas (2010)
  • Author(s): Kato H, Kagami Y, Nakagawa M, Karnan S, Yatabe Y, Nakamura S, Morishima Y, Seto M
  • Journal Title: The Open Leukemia Journal Volume: 3 Pages: 60-68
  • Peer Reviewed
• [Journal Article] Enteropathy-associated T-cell lymphoma--a clinicopathologic and array comparative genomic hybridization study (2010)
  • Author(s): Ko YH
  • Journal Title: Human Pathology Volume: 41巻 Pages: 1231-1237
  • Peer Reviewed
• [Presentation] A mutation in a single BRCA1 allele leads to genomic instability in human breast epithelial cells (2011)
  • Author(s): Konishi H
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(愛知県)
  • Year and Date: 2011-10-04
• [Presentation] ヒト体細胞株におけるPIGA遺伝子を利用した遺伝子ターゲッティング効率定量系の作成 (2011)
  • Author(s): シバスンダラン・カルナン
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 国立京都国際会館(京都府)
  • Year and Date: 2011-09-24
• [Presentation] BRCA1ヘテロ変異によってヒト乳腺上皮細胞にゲノム不安定性が発生する (2011)
  • Author(s): 小西裕之
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 国立京都国際会館(京都府)
  • Year and Date: 2011-09-22
• [Presentation] ヒト培養細胞遺伝子改変の新しい技術を用いた癌関連遺伝子の機能解析 (2010)
  • Author(s): 小西裕之
  • Organizer: 第33回日本分子生物学会年会第83回日本生化学会大会合同大会
  • Place of Presentation: 神戸国際展示場(兵庫県)
  • Year and Date: 2010-12-07
• [Presentation] ヒト培養細胞遺伝子改変の新しい技術を用いた癌関連遺伝子の機能解析 (2010)
  • Author(s): 小西裕之
  • Organizer: 第83回日本生化学会大会
  • Place of Presentation: 神戸国際展示場(兵庫県)
  • Year and Date: 2010-12-07
• [Presentation] ヒト培養細胞遺伝子改変の新技術を用いた癌関連遺伝子の機能解析 (2010)
  • Author(s): 小西裕之
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場(大阪府)
  • Year and Date: 2010-09-22
• [Presentation] ヒト培養細胞遺伝子改変の新技術を用いた癌関連遺伝子の機能解析 (2010)
  • Author(s): 小西裕之
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 第69回日本癌学会学術総会
  • Year and Date: 2010-09-22