BRCA1 is a key regulator of breast differentiation through activation of Notch signalling with implication for anti-endocrine treatment of breast cancers

報告日期: 2014/04/25
報告時間: 5:10/6:00
報告學生: 鍾校木
講評老師: 沈延盛
附件下載: 下載[1401-1396958509-1.pdf] 

BRCA1 is a key regulator of breast differentiation through activation of Notch signalling with implications for anti-endocrine treatment of breast cancers

Nucleic Acids Research, 2013, Vol.41, No.18 8601-8614

 

Student : 鍾校木                               Commentator : 沈延盛老師

Time : 2014/04/25                                  Location : Room 602

 

Abstract:

 

   BRCA 1(Breast cancer type 1 susceptibility protein) is a human tumor suppressor gene and normally expressed in breast and ovarian cells. BRCA 1 have multiple function including cell cycle checkpoint control, DNA damage repair, protein ubiquitination and transcription regulation. BRCA1 mutation results in loss of DNA repair function and increased the high risk of developing breast cancer. Recent study indicates that Notch pathway is important in the development and differentiation of multiple tissues and deletion of notch pathway signaling promotes cancer development. Interesting, authors of this study found that the BRCA 1 gene activates notch signaling pathway though transcription regulation in both breast normal and cancer cells. Specifically, BRCA 1 was shown to regulate the expression of notch ligand JAG1 though activation of delta-Np63 expression. Knockdown of notch ligands, BRCA1 and delta-Np63 was shown to promote tumoursphere growth, increases ALDH1 activity, induces ER-alpha receptor down-regulation and reduces the sensitivity to anti-estrogen drug. In conclusion, this study reveals that BRCA 1 transcriptional upregulation of notch signaling plays important roles in the normal differentiation process of breast tissue.

ALDH 1 : stem cell marker, Aldehyde Dehydrogenase 1.

 

Reference:

1.     King,M.C., Marks,J.H. and Mandell,J.B. (2003) Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science, 302, 643–646.

2.     Bouras,T., Pal,B., Vaillant,F., Harburg,G., Asselin-Labat,M.L., Oakes,S.R., Lindeman,G.J. and Visvader,J.E. (2008) Notch signaling regulates mammary stem cell function and luminal cell-fate commitment. Cell Stem Cell, 3, 429–441.