Specifically, mouse models of a 'triple-negative' breast cancer (utilizing conditional knockout of BRCA1 and p53 in the breast), of an endometrioid ovarian cancer (based on oncogenic kras and loss of function of pten), and of anatomic and functional consequences of BRCA1 mutations in granulosa cells, have led to further inquiry into the pathogenesis and therapeutic consequences of genetic alterations.
Tumor specimens from patients with TNBC were engrafted into humanized mammary fat pads of immunodeficient mice to create 3 independent human-in-mouse TNBC lines: 1 WT (WU-BC3) and 2 mutant for TP53 (WU-BC4 and WU-BC5).
In particular, TP53 mutations are exceptionally frequent and apparently among the key driving factors in triple negative breast cancer -the most aggressive breast cancer subgroup-whose management still represents a clinical challenge.
Within the triple-negative breast cancer subset, cell lines with a p53 mutation and increased p53 expression were more sensitive to the cytotoxic and proapoptotic effects of ENMD-2076 exposure than cell lines with decreased p53 expression.
The high frequency of TP53 mutations in triple negative breast cancer (TNBC: negative for estrogen receptor, progesterone receptor, and HER2) make Chk1 an attractive therapeutic target.
BRCA-1 methylation and TP53 mutation in triple-negative breast cancer patients without pathological complete response to taxane-based neoadjuvant chemotherapy.
A recent molecular and mutational analysis of breast cancers revealed that inactivation of tumor suppressors, p53 and PTEN, are strongly associated with triple negative breast cancer.
Human triple-negative breast cancer (TNBC) tumor samples with coinactivation of p53 and ARF exhibit high expression of both STAT1 and ISG15, and TNBC cell lines are sensitive to STAT1 depletion.
Only lymph node status was marginally significantly associated with poor prognosis of TNBC (P = 0.054), whereas other clinicopathological factors, including age, tumor size, histological grade, lymphovascular invasion, P53 status, Ki-67 index, and type of surgery, were not.
Here, we used the high prevalence of TP53 mutations in triple negative breast cancer (TNBC) to compare ctDNA and CTC detection rates and prognostic value in metastatic TNBC patients.
Primary mouse mammary epithelial cells (mMEC) with defined genetic features were used to delineate the combined action of RB and/or p53 in the genesis of TNBC.
Gain-of-function mutations in TP53 are a frequent occurrence in TNBC and have been demonstrated to repress apoptosis and up-regulate cell cycle progression.
The expression of p53 was higher in luminal B, HER2-enriched, and triple-negative breast cancers, and this was positively correlated with the expression of EGFR in TNBC but not in the other subtypes. p53 and EGFR expression was positively correlated in TNBC, which enables us to explore the molecular biological characteristics of TNBC, so as to provide new ideas for the treatment of TNBC.
The expression of CK5/6, AR, and p53 in formalin-fixed and paraffin-embedded (FFPE) surgical sections from 52 patients with TNBC was analysed by immunohistochemistry (IHC) and the co-expression patterns in individual cells were investigated by immunofluorescent (IF) staining.