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SILAC proteomics analysis to assess differences in protein expression upon BRCA2 inactivation

ABSTRACT: BRCA2 maintains genome stability by facilitating DNA repair via homologous recombination and replication fork stability. Loss of BRCA2 is deleterious for survival of normal cells, but is paradoxically tolerated in cancer cells. Using quantitative mass-spectrometry, differences in protein expression were identified that might shed light on how breast cancer cells (HCC38) survive in the absence of BRCA2.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Cell Culture

DISEASE(S): Breast Cancer

SUBMITTER: Francien Talens

LAB HEAD: Marcel A T M van Vugt

PROVIDER: PXD007253 | Pride | 2018-12-19

REPOSITORIES: Pride

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BRCA2 deficiency instigates cGAS-mediated inflammatory signaling and confers sensitivity to tumor necrosis factor-alpha-mediated cytotoxicity.

Heijink Anne Margriet AM Talens Francien F Jae Lucas T LT van Gijn Stephanie E SE Fehrmann Rudolf S N RSN Brummelkamp Thijn R TR van Vugt Marcel A T M MATM

Nature communications 20190109 1

Loss of BRCA2 affects genome stability and is deleterious for cellular survival. Using a genome-wide genetic screen in near-haploid KBM-7 cells, we show that tumor necrosis factor-alpha (TNFα) signaling is a determinant of cell survival upon BRCA2 inactivation. Specifically, inactivation of the TNF receptor (TNFR1) or its downstream effector SAM68 rescues cell death induced by BRCA2 inactivation. BRCA2 inactivation leads to pro-inflammatory cytokine production, including TNFα, and increases sens ...[more]

PMID: 30626869

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