2012 Fiscal Year Final Research Report
Characterization of human BRCA1 heterozygous knockout cell lines created by somatic cell gene targeting
| Project/Area Number |
22500999
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Carcinogenesis
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| Research Institution | Aichi Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
HOSOKAWA Yoshitaka 愛知医科大学, 医学部, 教授 (60229193)
SIVASUNDARAM Karnan 愛知医科大学, 医学部, 助教 (30557096)
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| Project Period (FY) |
2010 – 2012
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| Keywords | BRCA1 / ハプロ不全 / ゲノム不安定性 |
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| Research Abstract |
To assess the role for heterozygous BRCA1 inactivation in breast carcinogenesis, we created BRCA1 heterozygous knockout clones by targeting the BRCA1 gene in noncanceroushuman breast epithelial cell lines. These clones demonstrated impaired DNA repair via homologous recombination, hypersensitivity to genotoxic agents, and genomic instability, but exhibited no properties of transformed cells. These data suggest that haploinsufficiency caused by BRCA1 heterozygous mutation does not directly lead to cellular transformation or tumor development, but may be involved in the initiation of breast carcinogenesis.
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[Journal Article] The growth response to androgen receptor signaling in ERalpha-negative human breast cells is dependent on p21 and mediated by MAPK activation.2012
Author(s)
Garay JP, Karakas B, Abukhdeir AM, Cosgrove DP, Gustin JP, Higgins MJ, Konishi H, Konishi Y, Lauring J, Mohseni M, Wang GM, Jelovac D, Weeraratna A, Sherman Baust CA, Morin PJ, Toubaji A, Meeker A, De Marzo AM, Lewis G, Subhawong A, Argani P, Park BH.
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Journal Title
Breast Cancer Res
Volume: 14
Pages: R27
DOI
Peer Reviewed
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[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.
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Journal Title
Proc Natl Acad Sci U S A
Volume: 108
Pages: 17773-8
DOI
Peer Reviewed
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[Journal Article] PIK3CA mutations and EGFR overexpression predict for lithium sensitivity in human breast epithelial cells.2011
Author(s)
Higgins MJ, Beaver JA, Wong HY, Gustin JP, Lauring JD, Garay JP, Konishi H, Mohseni M, Wang GM, Cidado J, Jelovac D, Cosgrove DP, Tamaki A, Abukhdeir AM, Park BH.
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Journal Title
Cancer Biol Ther
Volume: 11
Pages: 358-67
DOI
Peer Reviewed
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[Journal Article] Knock in of the AKT1 E17K mutation in human breast epithelial cells does not recapitulate oncogenic PIK3CA mutations.2010
Author(s)
Lauring J, Cosgrove DP, Fontana S, Gustin JP, Konishi H, Abukhdeir AM, Garay JP, Mohseni M, Wang GM, Higgins M, Gorkin D, Reis M, Vogelstein B, Polyak K, Cowherd M, Buckhaults PJ, Park BH.
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Journal Title
Oncogene
Volume: 29
Pages: 2337-45
DOI
Peer Reviewed
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