Genetic interactions among Brca1, Brca2, Palb2, and Trp53 in mammary tumor development Journal Article

   


Authors: Huo, Y.; Selenica, P.; Mahdi, A. H.; Pareja, F.; Kyker-Snowman, K.; Chen, Y.; Kumar, R.; Da Cruz Paula, A.; Basili, T.; Brown, D. N.; Pei, X.; Riaz, N.; Tan, Y.; Huang, Y. X.; Li, T.; Barnard, N. J.; Reis-Filho, J. S.; Weigelt, B.; Xia, B.
Article Title: Genetic interactions among Brca1, Brca2, Palb2, and Trp53 in mammary tumor development
Abstract: Inherited mutations in BRCA1, BRCA2, and PALB2 cause a high risk of breast cancer. Here, we conducted parallel conditional knockout (CKO) of Brca1, Palb2, and Brca2, individually and in combination, along with one copy of Trp53, in the mammary gland of nulliparous female mice. We observed a functional equivalence of the three genes in their basic tumor-suppressive activity, a linear epistasis of Palb2 and Brca2, but complementary roles of Brca1 and Palb2 in mammary tumor suppression, as combined ablation of either Palb2 or Brca2 with Brca1 led to delayed tumor formation. Whole-exome sequencing (WES) revealed both similarities and differences between Brca1 and Palb2 or Brca2 null tumors. Analyses of mouse mammary glands and cultured human cells showed that combined loss of BRCA1 and PALB2 led to high levels of reactive oxygen species (ROS) and increased apoptosis, implicating oxidative stress in the delayed tumor development in Brca1;Palb2 double CKO mice. The functional complementarity between BRCA1 and PALB2/BRCA2 and the role of ROS in tumorigenesis require further investigation. © 2021, The Author(s).
Journal Title: npj Breast Cancer
Volume: 7
ISSN: 2374-4677
Publisher: Nature Publishing Group  
Date Published: 2021-04-23
Start Page: 45
Language: English
DOI: 10.1038/s41523-021-00253-5
PROVIDER: scopus
PMCID: PMC8065161
PUBMED: 33893322
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85104897989&doi=10.1038%2fs41523-021-00253-5&partnerID=40&md5=0be45b0bb931eec94c8e698c7a82400b
Notes: Article -- Export Date: 1 June 2021 -- Source: Scopus
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MSK Authors
  1. Nadeem Riaz
    418 Riaz
  2. Xin Pei
    134 Pei
  3. Britta Weigelt
    633 Weigelt
  4. Jorge Sergio Reis-Filho
    639 Reis-Filho
  5. Arnaud Fabian Da Cruz Paula
    145 Da Cruz Paula
  6. Fresia Gilda Pareja Zea
    217 Pareja Zea
  7. Thais Basili De Oliveira
    29 Basili De Oliveira
  8. Pier Selenica
    190 Selenica
  9. Rahul Kumar
    23 Kumar
  10. David Norman Brown
    91 Brown
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