Identification of BARD1 splice-isoforms involved in human trophoblast invasion

Article Article scientifique Article Identification of BARD1 splice-isoforms involved in human trophoblast invasion eng 2007 author Li Lin 636904 author Cohen Marie-Benoîte 0000-0003-4621-5464 135615 author Wu Jianyu author Sow Mamadou Hady author Nikolic Branka author Bischof Paul 26504 author Irminger-Finger Irmgard 1659-1672 10.1016/j.biocel.2007.04.018 17556008 1357-2725 The tumor suppressor protein BARD1, originally discovered as BRCA1-binding protein, acts in conjunction with BRCA1 as ubiquitin ligase. BARD1 and BRCA1 form a stable heterodimer and dimerization, which is required for most tumor suppressor functions attributed to BRCA1. In addition, BARD1 has BRCA1-independent functions in apoptosis, and a role in control of tissue homeostasis was suggested. However, cancer-associated mutations of BARD1 are rare; on the contrary, overexpression of truncated BARD1 was found in breast and ovarian cancer and correlated with poor prognosis. Here we report that human cytotrophoblasts, which show a strong similarity with cancer cells in respect of their invasive behavior and capacity of matrix metalloprotease production, overexpress isoforms of BARD1 derived from differential splicing. We demonstrate that expression of BARD1 and its isoforms is temporally and spatially regulated by human chorionic gonadotropin and by hypoxia, both factors known to regulate the invasive phase and proliferation of cytotrophoblasts. Interestingly, we found a subset of BARD1 isoforms secreted by cytotrophoblasts. BARD1 repression by siRNAs, mitigates the interference of cytotrophoblasts with cell adhesion of collagen matrix-dependent epithelial cells, suggesting a role of BARD1 isoforms in extracellular matrix remodelling and in cytotrophoblasts invasion. Alternative Splicing/genetics Cell Adhesion Cell Line, Tumor Cell Movement Choriocarcinoma/pathology Chorionic Gonadotropin/genetics/metabolism Collagen/metabolism Female Humans Immunohistochemistry Pregnancy Pregnancy Trimester, First Protein Isoforms/chemistry/genetics/secretion Trophoblasts/cytology/metabolism Tumor Suppressor Proteins/chemistry/genetics/secretion Ubiquitin-Protein Ligases/chemistry/genetics/secretion Dewey 618 58 Département de pédiatrie, gynécologie et obstétrique 223 false 584 Laboratoire de biologie des tumeurs gynécologiques et du développement 927 International journal of biochemistry & cell biology 39 9 d0825caf-2969-48de-8501-9a1f51d8103d Article (Published version) Restricted 1-s2.0-S1357272507001288-main.pdf 2537348 application/pdf restrictedAccess Faculté de médecine / Section de médecine clinique / Département de pédiatrie, gynécologie et obstétrique

Title	Published in	Year	Views	Downloads

Identification of BARD1 splice-isoforms involved in human trophoblast invasion	International journal of biochemistry & cell biology	2007	564	0
L'expression de BARD1 et sa fonction potentielle dans le cancer = (Expression of BARD1 isoforms and possible function in cancer)		2007	1,142	722

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Li, Lin