Fig. 5: Notch1 activation rescues the lethal effect caused by BRCA1 deficiency through the ATR–CHK1 axis.
From: NOTCH1 activation compensates BRCA1 deficiency and promotes triple-negative breast cancer formation
a Western blotting analysis of cell-cycle checkpoint proteins at different time points after Dox administration. b Western blotting analysis of CHK1 phosphorylation after ICN1 induction after knockdown of CHK1. c MI assay of MCF10A cells when CHK1 was knocked down with/without ICN1 overexpression. Cells were collected at 1 h after 0.5 Gy irradiation treatment; n = 3 biologically independent experiments. d MTT assay evaluating the rescue effect of Brca1 acute knockdown on the 3rd day when CHK1 was knocked down with shRNA; n = 3 biologically independent experiments. e Western blotting analysis of CHK1 phosphorylation after ICN1 induction following ATR knockdown. f MI assay of MCF10A cells when ATR was knocked down with/without ICN1 overexpression. Cells were collected at 1 h after 0.5 Gy irradiation treatment; n = 3 biologically independent experiments. g MTT assay evaluating the rescue effect of Brca1 acute knockdown on the 3rd day after ATR knockdown with shRNA; n = 3 biologically independent experiments. h IP analysis indicated that ICN1 can directly bind with ATR. i, j Immunohistochemistry staining of a human TNBC patient tissue microarray for target proteins. The scatter plots indicate a positive correlation between ICN1 and p-ATR (n = 90 for i, n = 72 for j); R and p-values were obtained based on Spearman’s rank correlation coefficient R’s and probability (p) value calculator. Data are presented as mean values ± s.d.
