BRCA2 suppresses cell proliferation via stabilizing MAGE-D1

Xin Xia Tian, Deepak Rai, Jun Li, Chaozhong Zou, Yujie Bai, David Wazer, Vimla Band, Qingshen Gao

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

Germ line mutations in BRCA2 gene predispose women to early-onset familial breast and ovarian cancer. BRCA2 is a protein of multiple functions. In addition to its role in DNA double-strand break repair, BRCA2 also plays a role in stabilization of stalled DNA replication forks, cytokinesis, transcription regulation, mammalian gametogenesis, centro-some duplication, and suppression of cell proliferation. However, how BRCA2 mutations predispose women specifically to breast and ovarian cancer remains undefined. Here we found that BRCA2 binds and stabilizes MAGE-D1, a member of the MAGE gene family of proteins. Expression of BRCA2 and MAGE-D1 synergistically suppresses cell proliferation independently of the p53 pathway. Using two MAGE-D1 RNA interferences and two cell lines expressing low or undetectable levels of MAGE-D1, we further showed that the expression of MAGE-D1 is required for BRCA2-mediated suppression of cell proliferation, indicating that MAGE-D1 is a downstream target of BRCA2 and that BRCA2 suppresses cell proliferation via stabilizing MAGE-D1. Importantly, MAGE-D1 protein expression was reduced in 6 of 16 breast carcinoma cell lines tested as compared with untransformed immortal mammary epithelial cell lines, suggesting that suppression of MAGE-D1 expression may be involved in the tumorigenesis of a subset of sporadic breast cancers.

Original languageEnglish (US)
Pages (from-to)4747-4753
Number of pages7
JournalCancer Research
Volume65
Issue number11
DOIs
StatePublished - Jun 1 2005

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Tian, X. X., Rai, D., Li, J., Zou, C., Bai, Y., Wazer, D., Band, V., & Gao, Q. (2005). BRCA2 suppresses cell proliferation via stabilizing MAGE-D1. Cancer Research, 65(11), 4747-4753. https://doi.org/10.1158/0008-5472.CAN-05-0018