Biomedical subjects

Yves-Jean Bignon

Publications and source records attributed to Yves-Jean Bignon.

22 records · Page 2Linked to original sources

PubMed2002

Dominant-negative activity of a Brca1 truncation mutant: effects on proliferation, tumorigenicity in vivo, and chemosensitivity in a mouse ovarian cancer cell line.

In order to generate an in vitro mouse model for the study of human ovarian cancers, we compared the effects of a truncated Brca1 mutant expression on cellular phenotype with those of a full-length sense and antisense Brca1 expression in the ID-8 mouse epithelial ovarian cancer cell line. The examined cellular processes include proliferation, tumorigenicity in syngeneic mice in vivo and sensitivity/resistance to several cytotoxic drugs. We found that the expression of a spontaneous truncated Brca1 mutant in ID-8 cells which contain two endogenous wild-type Brca1 alleles led to a dominant-negative effect of Brca1, demonstrated by an increase in tumorigenicity in vivo and in chemosensitivity. Expression of a truncated Brca1 mutant in a mouse epithelial ovarian cancer cell line could thus provide a powerful in vitro model for the study of human BRCA1-related ovarian tumorigenesis.

Animals↗

PubMedDate not supplied

Nijmegen breakage syndrome gene (NBS1) is not the tumor suppressor gene at 8q21.3 involved in colorectal carcinoma.

Genetic instability is characteristic of cancer cells, both at the chromosomal level (e.g., aneuploidy, aneusomy, translocations), and at the sequence level (e.g., microsatellite instability). Colorectal cancers (CRCs) can be divided into two groups: tumors of the proximal colon, where microsatellite instability is frequent and chromosomal aberrations are rare, and tumors of the distal colon, where microsatellite instability is less frequent and chromosomal aberrations are common. Constitutional chromosomal instability is a hallmark of the Nijmegen breakage syndrome (NBS), a disorder in which the NBS1 gene is mutated. In a previous study, we found an elevated frequency of allelic imbalance (AI) at the 8q21.3 NBS1 locus in proximal, though not distal CRCs. This result suggested that the loss of NBS1 might contribute to the genetic instability, and thus the malignant progression, of proximal CRC. We therefore sequenced the 16 exons of the NBS1 gene in all cases where we had observed AI. Of the 29 cases, none showed any sequence anomaly, although several polymorphisms were found. We also studied markers flanking the recently described Rad54B gene, which is a member of the Rad52 epistasis group to which NBS1 itself belongs. Mutations of this gene, located a few cM distal to NBS1, have been found in colorectal cancer and in primary lymphomas, and it may thus be the target of AI at 8q21. We found that AI at Rad54B was not frequent, and none was observed in cases showing AI at NBS1.

Adult↗

PubMedDate not supplied

Expression of BRCA1 and BRCA2 in male breast cancers and gynecomastias.

BRCA1 and BRCA2 breast cancer susceptibility genes are responsible for most of the hereditary breast cancers. Mutations in BRCA1 account for up to 40-50% of families with hereditary breast cancer only. Mutations in BRCA2 are linked to the other half of inherited breast cancer families and also to male breast cancer. On the contrary, no sporadic breast tumors have been shown to harbor mutations in BRCA1 and BRCA2 genes. It seems that altered expressions of BRCA1 and BRCA2 genes may contribute to breast cancer development. Moreover, BRCA1 and BRCA2 expressions are regulated in human breast cancer cell lines by estrogen. We addressed the issue of BRCA1 and BRCA2 expression in male breast cancers and gynecomastias. We investigated the presence of BRCA1 and BRCA2 proteins in male breast specimens by immunohistochemical analysis with a panel of antibodies elicited against BRCA1 and BRCA2. The specificity of each antibody has been verified by Western blotting in cell lines from different origins. The characterization of 6 anti-BRCA1 antibodies revealed a BRCA1 200-kDa protein detected in breast cell lines (MDA-MB 231, HBL 100, T-47D and MCF7) or in an acute leukemia (MOLT 4), known to overexpress BRCA1. All 5 anti-BRCA2 antibodies detected a BRCA2 384-kDa protein in the HBL100 and MCF7 breast cell lines. By immunohistochemistry, we found nuclear, perinuclear, endoplasmic reticulum, Golgi vesicle, secretion and apical cytoplasmic stainings in gynecomastias and sporadic and hereditary male breast cancers, for BRCA1 and BRCA2 protein expressions. We report an extensive expression of BRCA1 and BRCA2 proteins in different compartments of the mammary gland cells in male breast carcinomas and gynecomastias. This is consistent with the estrogen-dependent expression of BRCA1 and BRCA2 in human breast cells.

Adolescent↗

PubMedDate not supplied

Differential expressions of BRCA1 and BRCA2 in infantile gynecomastia.

BRCA1 and BRCA2 breast cancer susceptibility genes are responsible for most of the hereditary breast cancers. No or very few sporadic breast tumors have been shown to harbor mutations in the coding sequence of BRCA1 or BRCA2. In contrast to normal breast epithelial cells, BRCA1 mRNA levels in tumors appeared to be down-regulated by methylation, while BRCA2 showed significant overexpression in sporadic breast cancers. We report herein an infantile gynecomastia in a two-year-old boy, studied by immunohistochemistry of anti-BRCA1 and anti-BRCA2 antibodies. We demonstrated that BRCA1 proteins, like BRCA2, are widely expressed in the nuclei of epithelial cells surrounding the lumen of the ducts in infantile gynecomastia. The intensive nuclear staining of both proteins in the mammary tissues means that BRCA1 and BRCA2 proteins are largely expressed in infantile gynecomastia.

BRCA1 Protein↗