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See detailDifferent mechanisms are implicated in ERBB2 gene overexpression in breast and in other cancers
Vernimmen, D.; Guéders, Maud ULg; Pisvin, Sonia ULg et al

in British Journal of Cancer (2003), 89(5), 899-906

The ERBB2 gene is overexpressed in 30% of breast cancers and this has been correlated with poor prognosis. ERBB2 is upregulated in other cancers such as prostate, pancreas, colon and ovary. In breast ... [more ▼]

The ERBB2 gene is overexpressed in 30% of breast cancers and this has been correlated with poor prognosis. ERBB2 is upregulated in other cancers such as prostate, pancreas, colon and ovary. In breast cancer cells, the mechanisms leading to ERBB2 gene overexpression are increased transcription and gene amplification. In these cancers, AP-2 transcription factors are involved in ERBB2 overexpression, and AP-2 levels are correlated with p185(c-erbB-2) levels. In this work, we wanted to know if the same molecular mechanisms are responsible for the ERBB2 upregulation in non-breast cancers. We compared ERBB2 gene copy number, p185(c-erbB-2) and mRNA levels with AP-2 levels in several ovary, prostate, colon and pancreas cancer cells. A moderate expression of erbB-2 mRNA and protein were observed in some cells without gene amplification. In contrast to breast cancer cells, AP-2 factors were absent or low in some non-breast cells which did express ERBB2. It is thus likely that AP-2 is not a major player in the increased levels of erbB-2 transcripts in non-breast cancer cells. The transcriptional activity of the ERBB2 promoter in colon and ovary cancer cells was estimated using reporter vectors. The results showed that the promoter regions involved in ERBB2 gene overexpression in breast cancer cells are different from those that lead to the gene upregulation in colon and ovary cancers. In conclusion, our results indicate that different transcriptional and post-transcriptional mechanisms are responsible for the increased levels of erbB-2 transcript and protein in breast and non-breast cancer cells. [less ▲]

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See detailIL10 production in cultures of lymphocytes derived from biopsies of normal exocervix, transformation zone and squamous intraepithelial lesion
Jacobs, Nathalie ULg; Renard, Isabelle; Pisvin, Sonia ULg et al

in Monsonego, J. (Ed.) 4th International Multidisciplinary Congress - Eurogin 2000 (2000)

The immune system appears to play a role in the development of squamous intraepithelial lesions (SIL) and their progression to cancer. We have developed a technique to isolate and cultivate lymphocytes ... [more ▼]

The immune system appears to play a role in the development of squamous intraepithelial lesions (SIL) and their progression to cancer. We have developed a technique to isolate and cultivate lymphocytes either from the epithelium or from the underlying stroma of small biopsies from the normal exocervix, the transformation zone (TZ) and SIL. The majority of cells derived from the epithelium of all biopsies were CD8+ T cells. No major difference was observed for the lymphocyte phenotype. Among all cytokines tested by ELISA (IL10, IL4 and IFNγ), only IL10 was significantly higher in the TZ in comparison with the exocervix. In cultures derived from the stroma, a decreased percentage in T cells was observed in the TZ and SIL in comparison with the exocervix. This decrease in T cells concerned CD8+ (SIL) and TCRγδ+ T cells (TZ and SIL). We did not observe any difference in IL10 or IL4 production, although patients with SIL produced more IFNγ. The higher levels of IL10 production by lymphocytes derived from the epithelium of the TZ might contribute to the predisposition of this region to cervical carcinogenesis. [less ▲]

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