Abstract
Chk1, along with Chk2, regulates processes such as DNA replication, cell cycle control, chromatin restructuring and apoptosis. DNA damage/replication stress activates Chk1 by phosphorylation from the PI3/PI4 family of kinases. Activation of Chk1 is thought to be mediated by proteins containing the BRCA1 C-terminal domain (BRCT). We previously identified a potential complex of four Chk1-associated proteins by immunoprecipitation, western blotting and mass spectrometry, one of which is BRCA1. Germline mutations in BRCA1 are responsible for many cases of hereditary breast cancer, and cells deficient in BRCA1 sustain spontaneous aberrations in chromosome structure. Such findings indicate that BRCA1 is essential for suppressing genome instability.
Highlights
Ten to twenty per cent of breast tumours exhibit a basallike genetic profile and these tumours carry a poor prognosis
We have modelled the effects of polygenic predisposition in the East Anglian population, and have shown that the model predicts a wide distribution of individual risk in the population, such that half of all breast cancers may occur in the 12% of women at greatest risk
No single gene so far identified contributes more than 2% of the total inherited component, consistent with a model in which susceptibility is the result of a large number of individually small genetic effects
Summary
Ten to twenty per cent of breast tumours exhibit a basallike genetic profile and these tumours carry a poor prognosis. BRCA1 is a tumour suppressor gene which is mutated in up to 5–10% of breast cancer cases and is involved in multiple cellular processes including DNA damage control, cell cycle checkpoint control, apoptosis, ubiquitination and transcriptional regulation. Results We have previously carried out microarray-based expression profiling to examine differences in gene expression when BRCA1 is reconstituted in BRCA1 mutated HCC1937 breast cancer cells. We aim (i) to investigate the expression of the whole family of IAPs across a wide range breast cancer cell lines and tumour samples at both the RNA and protein level, and (ii) to determine whether targeting IAPs alters susceptibility to apoptosis. This study tested the hypothesis that Brk is involved in regulating the tumour cell environment during progression and investigated the effects of suppressing Brk in breast carcinoma cells to determine in which contexts Brk may be a valid therapeutic target. Molecular and clinical evidence points to a role for TGFβ signalling in cancer progression and metastasis; it is unclear at which points of the metastatic process TGFβ signalling occurs and whether it is necessary and/or sufficient to elicit cancer cell motility
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
