Brca1-deficient murine mammary epithelial cells have increased sensitivity to CDDP and MMS

被引:47
作者
Sgagias, MK
Wagner, KU
Hamik, B
Stoeger, S
Spieker, R
Huber, LJ
Chodosh, LA
Cowan, KH
机构
[1] Univ Nebraska, Med Ctr, Eppley Inst Res Canc & Allied Dis, Omaha, NE 68198 USA
[2] Univ Penn, Sch Med, Dept Canc Biol, Philadelphia, PA 19104 USA
[3] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA
[4] Univ Penn, Sch Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA
关键词
Bcra1-deficiency; DNA-damage and repair; breast cancer; CDDP; MMS;
D O I
10.4161/cc.3.11.1211
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
In this report we describe the isolation of an isogenic pair of Brca1(++) and Brca1(-/-) murine mammary epithelial cells (MMECs). These cells were isolated from Brca1 conditional knock-out mice which contained loxP sites flanking exon 11 of the Brca1 gene (Brca1(f1/f1)) and then immortalized by infection with HPV-16E6 retrovirus to degrade p53 protein. Brca1-/- MMECs were generated by deletion of exon 11 following transduction of Brca1(f1/f1) MMECs with a retroviral vector expressing Cre recombinase. Brca1-deficiency rendered MMECs sensitive to cis-platinum (II) diamine dichloride ( CDDP) and methylmethane sulfonate (MMS). The Brca1(+/+) and Brca1(-/-) MMECs is the only known pair of isogenic mammary epithelial cell lines. The understanding of the mechanisms of the CDDP sensitivity of the BRCA1-deficient mammary epithelial cells would be very important in understanding how BRCA1-deficiency plays a role in tissue specific breast cancer chemotherapy. These studies support the role of BRCA1 in the CDDP-induced and MMS-induced DNA damage and repair by p53-independent pathways.
引用
收藏
页码:1451 / 1456
页数:6
相关论文
共 48 条
  • [11] Ubiquitination and proteasomal degradation the BRCA1 tumor suppressor is regulated during cell cycle progression
    Choudhury, AD
    XuO, H
    Baer, R
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (32) : 33909 - 33918
  • [12] Requirement of ATM-dependent phosphorylation of BRCA1 in the DNA damage response to double-strand breaks
    Cortez, D
    Wang, Y
    Qin, J
    Elledge, SJ
    [J]. SCIENCE, 1999, 286 (5442) : 1162 - 1166
  • [13] Cressman VL, 1999, MOL CELL BIOL, V19, P7061
  • [14] Deng CX, 2000, BIOESSAYS, V22, P728
  • [15] Role of the tumor suppressor gene Brca1 in genetic stability and mammary gland tumor formation
    Deng, CX
    Scott, F
    [J]. ONCOGENE, 2000, 19 (08) : 1059 - 1064
  • [16] Developmental studies of Brca1 and Brca2 knock-out mice
    Hakem, R
    de la Pompa, JL
    Mak, TW
    [J]. JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA, 1998, 3 (04) : 431 - 445
  • [17] Involvement of two endonuclease III homologs in the base excision repair pathway for the processing of DNA alkylation damage in Saccharomyces cerevisiae
    Hanna, M
    Chow, BL
    Morey, NJ
    Jinks-Robertson, S
    Doetsch, PW
    Xiao, W
    [J]. DNA REPAIR, 2004, 3 (01) : 51 - 59
  • [18] Induction of GADD45 and JNK/SAPK-dependent apoptosis following inducible expression of BRCA1
    Harkin, DP
    Bean, JM
    Miklos, D
    Song, YH
    Truong, VB
    Englert, C
    Christians, FC
    Ellisen, LW
    Maheswaran, S
    Oliner, JD
    Haber, DA
    [J]. CELL, 1999, 97 (05) : 575 - 586
  • [19] BRCA1 induces DNA damage recognition factors and enhances nucleotide excision repair
    Hartman, AR
    Ford, JM
    [J]. NATURE GENETICS, 2002, 32 (01) : 180 - 184
  • [20] Impaired DNA damage response in cells expressing an exon 11-deleted murine Brca1 variant that localizes to nuclear foci
    Huber, LJ
    Yang, TW
    Sarkisian, CJ
    Master, SR
    Deng, CX
    Chodosh, LA
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 2001, 21 (12) : 4005 - 4015