Aberrant expression of BARD1 in breast and ovarian cancers with poor prognosis.

Abstract

Mutations in tumor-suppressor gene BARD1 have been found in inherited and spontaneous breast, ovarian and uterine cancers. BARD1 plays a critical role in DNA repair and ubiquitination as binding partner of BRCA1, with which it colocalizes to nuclear dots. Independently of BRCA1, BARD1 can induce p53-dependent apoptosis in response to genotoxic stress. Therefore, BARD1 or p53 might be defective in cancer cells spared from apoptosis. We investigated BARD1 and p53 expression in ovarian, breast and non-small-cell lung cancers. BARD1 expression was highly upregulated and cytoplasmic in most cancer cells, while weak nuclear staining was observed in the surrounding normal tissue. Maximal BARD1 expression was associated with the most malignant ovarian cancer, clear cell carcinoma. In breast cancer, BARD1 expression was correlated with poor differentiation and large tumor size, established factors of poor prognosis, as well as short disease-free survival. In contrast to breast and ovarian cancers, no correlation of BARD1 expression with either grade or stage could be determined for lung cancer. RT-PCR, performed on 10 ovarian cancers, revealed absence of the 5' portion of the BARD1 transcript in 7 tumors, and sequencing of the remaining 3 identified a missense mutation (A1291G) resulting in an amino acid change of glutamine 406 to arginine. These data suggest that genetic and epigenetic changes might lead to elevated cytoplasmic expression of BARD1 and that cytoplasmic BARD1 might be a poor prognostic factor for breast and ovarian cancers.

• Authors: Jian-Yu Wu, Anne-Therese Vlastos, Marie-Françoise Pelte, Maria-Adelaide Caligo, Andrea Bianco, Karl-Heinz Krause, Geoffrey J Laurent, Irmgard Irminger-Finger
• Journal: International journal of cancer (Int J Cancer) Vol. 118 Issue 5 Pg. 1215-26 (Mar 01 2006) ISSN: 0020-7136 [Print] United States
• PMID: 16152612 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: (c) 2005 Wiley-Liss, Inc.

Chemical References

• BRCA1 Protein
• Tumor Suppressor Protein p53
• Tumor Suppressor Proteins
• BARD1 protein, human
• Ubiquitin-Protein Ligases

Topics

• Adult
• Aged
• Aged, 80 and over
• BRCA1 Protein (genetics)
• Breast Neoplasms (diagnosis, genetics, metabolism, pathology)
• Carcinoma, Non-Small-Cell Lung (genetics, metabolism)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Middle Aged
• Mutation (genetics)
• Ovarian Neoplasms (diagnosis, genetics, metabolism, pathology)
• Prognosis
• Tumor Suppressor Protein p53 (metabolism)
• Tumor Suppressor Proteins (genetics, metabolism)
• Ubiquitin-Protein Ligases (genetics, metabolism)