Biomedical subjects

Y J Bignon

Publications and source records attributed to Y J Bignon.

114 records · Page 7Linked to original sources

PubMedDate not supplied

Cyclosporine A inhibition of prolactin-dependent up-regulation of BRCA1 protein expression in human breast cell lines.

BACKGROUND: Previously, we reported experimental evidence that BRCA1, breast and ovarian cancer susceptibility gene is up-regulated in response to Prolactin stimulation. In this work, we studied the effects of Cyclosporine A and the competition with Prolactin on BRCA1 protein expression in vitro. METHODS: The expression of BRCA1 was monitored in a human breast cancer cell line (MCF7) by comparison with a normal breast epithelial one (MCF10a) treated with Cyclosporine A and ovine Prolactin. The amount of BRCA1 protein expression was quantified using a strategy of two successive affinity perfusion chromatographies. RESULTS AND CONCLUSION: We showed that Prolactin in presence of Cyclosporine A has no effect on BRCA1 protein expression in human breast cell lines. This emphasized the hypothesis that BRCA1 may be stimulated by Prolactin.

BRCA1 Protein↗

PubMedDate not supplied

Regulation of BRCA1 and BRCA2 transcript in response to cisplatin, adriamycin, taxol and ionising radiation is correlated to p53 functional status in ovarian cancer cell lines.

Recent studies suggest that BRCA1 and BRCA2 expression, in response to cytotoxic agents, may be dependent on p53 status. To investigate this possibility, we quantified their transcripts in ovarian cancer cells, PA1 (wild-type p53), CaOV-3 (mutated p53) and SKOV-3 (null p53) exposed to four cytotoxic agents. In PA1, taxol and cisplatin had no effect, while adriamycin and ionising radiation (IR) induced both genes. In SKOV-3, expression decreased in response to taxol and cisplatin, and initially decreased then increased in response to adriamycin while IR had no effect. CaOV-3 responded similarly to SKOV-3, except for both genes being increased by cisplatin. We speculate that this regulation may be part of the survival response to certain cytotoxic agents and may be dependent in part on p53 status of cells.

Antineoplastic Agents↗

PubMedDate not supplied

Localization of human BRCA1 and BRCA2 in non-inherited colorectal carcinomas and matched normal mucosas.

We characterized the expression of BRCA1 and BRCA2 in 38 sporadic colorectal carcinomas and matched normal mucosas with 9 anti-BRCA1 antibodies and 4 anti-BRCA2 antibodies, raised against several different epitopes, using immunohistochemical technique. We demonstrated an increased BRCA1 and BRCA2 staining in the apical cell pole of epithelial malignant cells and we also revealed a significant increase in BRCA1 and BRCA2 nuclear foci in tumor colorectal specimens in comparison with corresponding normal tissues. These increases in BRCA1 and BRCA2 expression may be explained by the fact that colorectal tissue is subject to very active proliferation and differentiation.

Adult↗

PubMedDate not supplied

Quantitative analysis of BRCA1, BRCA2 and Hmsh2 mRNA expression in colorectal Lieberkühnien adenocarcinomas and matched normal mucosa: relationship with cellular proliferation.

The human DNA mismatch repair gene hMSH2 is involved in the development of sporadic and hereditary nonpolyposis colorectal cancer. An increased risk of colorectal cancer has also been suggested in BRCA1 and BRCA2 mutation carriers. To address the relationship between the expression level of these genes and colorectal tumorigenesis, we studied BRCA1, BRCA2 and hMSH2 mRNA expression by real-time quantitative RT-PCR in 72 colorectal Lieberkühnien adenocarcinomas and matched normal mucosa. We investigated the relationship between mRNA levels and various clinicopathological parameters. The mean expression of BRCA1 3' and BRCA2 3' (mRNA pool), BRCA1 ex11 (with exon 11), BRCA2 ex12 (with exon 12) and hMSH2 mRNAs were increased in tumor samples. BRCA1 and BRCA2 mRNAs expressions were altered according to colon tumor site: BRCA1 3' and BRCA2 3' mRNAs levels were highest, respectively, in the right colon and left colon. No difference in hMSH2 mRNA levels was detected in relation to clinicopathological parameters. The mean SPF value was significantly higher in tumor than in non-tumor colonic tissue, and a high SPF value was correlated with high BRCA2 mRNA levels. BRCA2 3' mRNA levels tended to decrease as the Dukes' stage increased. In conclusion, the mechanisms of colorectal carcinogenesis seem to differ according to the right or left position of the tumor.

Adenocarcinoma↗

PubMedDate not supplied

Antagonism of prolactin binding by cyclosporine A on MCF7 breast tumour cell line.

Cyclosporine A (an immunosuppressive cyclic undercapeptide) acts as an antagonist to prolactin receptors on a breast tumour cell line (MCF7) which is known to express specific prolactin receptors. The competition between cyclosporine A and prolactin to prolactin receptors was demonstrated by measuring the decreased specific 125I-labeled prolactin-binding to prolactin receptors in the presence of increasing concentrations of cyclosporine A. Moreover, cyclosporine A inhibiting effects on the cell growth were investigated in this mammary cancer (MCF) by measuring the cell DNA content with flow cytometry. Our results should prove very useful in understanding the mechanisms of prolactin regulation of DNA synthesis in tumorigenesis of the mammary gland.

Binding, Competitive↗

PubMedDate not supplied

Association between H-ras minisatellite and colorectal cancer risk.

BACKGROUND: The H-ras locus has been suggested to play an important role in susceptibility to cancer. However, the results remain controversial. METHODS: In order to elucidate the potential role of the H-ras locus in colorectal carcinogenesis, 142 colorectal tumors with matched normal samples were studied for genomic instability and loss of heterozygosity (LOH), and 143 healthy samples of white blood cell DNA were examined by PCR, for H-ras allelic polymorphism. RESULTS: Nine percent of colorectal cancer patients constitutionally presented at least one rare allele versus 1.4% of healthy individuals (P = 0.0034). The risk of developing colorectal cancer increased significantly with the presence of rare H-ras alleles (odds ratio = 7.10 and 95% confidence interval = 1.92-26.35). The genotype associating one common allele and one rare allele was overrepresented in cancer patients (P < 0.01). No associations were observed between the rare alleles and tumor site or with the aggressiveness of cancer. Low frequencies of LOH (5%) and genetic instability (0.7%) at the H-ras locus were found in our colorectal cancer set. CONCLUSIONS: Consequently, the presence of uncommon alleles at the H-ras locus appeared to be an informative genetic marker.

Adenocarcinoma↗