1,720,979 research outputs found
BARD1 is a target of miR-19a and miR-19b: a new selective epigenetic therapy for acute myeloid lekaemias?
No full text
Truncated isoforms of BRCA1-associated protein BARD1 are expressed in NSCLC and are potential targets for treatment
No full textMutations in the BRCA1 gene predispose carriers to breast and ovarian cancer, but are also associated
with sporadic cancers of other organs. BRCA1, as heterodimer with its protein binding partner
BARD1, has tumor suppressor functions in DNA repair and cell cycle control, due to the ubiquitin
ligase activity of the BRCA1-BARD1 complex. While formation of the BRCA1-BARD1 heterodimer
depends on the N-terminal RING fingers of both proteins, the C-terminus of the BARD1 has also a
function in mitosis. Interestingly, cancer cells express BARD1 isoforms that lack the RING finger and
repress full length (FL) BARD1. SiRNA depletion of isoforms in cancer cells deficient of FL BARD1
leads to growth arrest in vitro. Furthermore, an N-terminally truncated isoform, but not FL BARD1,
can bind to the mitotic kinase Aurora B, which is often upregulated in cancer. We investigated the role
of BARD1 isoforms in NSCLC. Immunohistochemistry and RT-PCR, performed on biopsies, showed
loss of BARD1 N-terminal epitopes and exons, respectively. Since the C-terminus of BARD1 is
involved in pro-proliferative functions through binding to Aurora B, we investigated whether
expression of BARD1 isoforms was correlated with Aurora B expression in NSCLC. Co-expression of
Aurora B and BARD1 isoforms was found in bronchoalveolar carcinoma. Our data demonstrate that
truncated BARD1 isoforms that are deficient of BRCA1-linked tumor suppressor functions are
expressed in NSCLC. Since BARD1 isoforms can interact with Aurora B in vitro, the co-expression of
truncated BARD1 and Aurora B in NSCLC suggests that they act in a common oncogenic pathway
Expression of oncogenic BARD1 isoforms affects colon cancer progression and correlates with clinical outcome.
No full textBACKGROUND:
Colon cancer predisposition is associated with mutations in BRCA1. BRCA1 protein stability depends on binding to BARD1. In different cancers, expression of differentially spliced BARD1 isoforms is correlated with poor prognosis and decreased patient survival. We therefore suspected a role of BARD1 isoforms in colon cancer.
METHODS:
We performed immunohistochemistry in 168 colorectal cancers, using four antibodies directed against differentially expressed regions of BARD1. We determined structure and relative expression of BARD1 mRNA isoforms in 40 tumour and paired normal peri-tumour tissues. BARD1 expression was correlated with clinical outcome.
RESULTS:
BARD1 isoforms were expressed in 98% of cases and not correlated with BRCA1. BARD1 mRNA isoforms were upregulated in all tumours as compared with paired normal peri-tumour tissues. Non-correlated expression and localisation of different epitopes suggested insignificant expression of full-length (FL) BARD1. Expression of N- and C-terminal epitopes correlated with increased survival, but expression of epitopes mapping to the middle of BARD1 correlated with decreased survival. Middle epitopes are present in oncogenic BARD1 isoforms, which have pro-proliferative functions. Correlated upregulation of only N- and C-terminal epitopes reflects the expression of isoforms BARD1δ and BARD1φ.
CONCLUSION:
Our results suggest that BARD1 isoforms, but not FL BARD1, are expressed in colon cancer and affect its progression and clinical outcome
HDAC Inhibitors Repress BARD1 Isoform Expression in Acute Myeloid Leukemia Cells via Activation of miR-19a and/or b
No full textOver the past years BARD1 (BRCA1-associated RING domain 1) has been considered as both a BRCA1 (BReast Cancer susceptibility gene 1, early onset) interactor and tumor suppressor gene mutated in breast and ovarian cancers. Despite its role as a stable heterodimer with BRCA1, increasing evidence indicates that BARD1 also has BRCA1-independent oncogenic functions. Here, we investigate BARD1 expression and function in human acute myeloid leukemias and its modulation by epigenetic mechanism(s) and microRNAs. We show that the HDACi (histone deacetylase inhibitor) Vorinostat reduces BARD1 mRNA levels by increasing miR-19a and miR-19b expression levels. Moreover, we identify a specific BARD1 isoform, which might act as tumor diagnostic and prognostic markers
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
- …
