Università degli Studi di Cagliari
Giovedì 19 giugno 2008, ore 17
Aula magna Chimica, Palazzo delle Scienze
19 giugno 2008
Università degli Studi di Cagliari
Dipartimento di Tossicologia
Sezione di Oncologia e Patologia Molecolare
"BARD1 goes wild without BRCA1: The tumor suppressor functions of the BARD1-BRCA1 heterodimer and oncogenic functions of cancer-associated isoforms"
Dr Irmgard IRMINGER
Head of Molecular Gynaecology and Obstetrics Laboratory, University Hospitals Geneva (CH)
Giovedì 19 giugno 2008, ore 17
Aula magna Chimica, Palazzo delle Scienze
Via Ospedale 72, Cagliari
The BARD1 protein is required for protein stability of the tumor suppressor BRCA1. The functions of BRCA1 depend on the ubiquitin ligase activity of the BRCA1-BARD1 heterodimer. The N-terminal RING domains of both proteins act as interaction modules and form a ubiquitin ligase, which has functions in DNA repair, cell cycle checkpoint regulation, and mitosis. A specific combination of isoforms, generated by differential splicing and alternative transcription initiation is expressed in gynaecological, but not in haematological cancer cell lines, and expression is correlated with advanced stage of cancer and with cancers of poor prognosis, suggesting a role of BARD1 isoforms in cancer progression. The function of BARD1 isoform expression in cancer cells is addressed with siRNA interference in ovarian and breast cancer cell lines. These experiments demonstrated that BARD1 is required for cell proliferation and that isoforms retain functions important for mitosis completion, similar to BRCA2. Thus BARD1 isoforms act as cancer maintenance genes and are targets for treatment.
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