Nadira M'rabet

Universität Basel, Basel, BS, Switzerland

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Publications (3)7.89 Total impact

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    ABSTRACT: Adamts17 is a member of a family of secreted metalloproteinases. In this report, we show that knockdown of Adamts17 expression induces apoptosis and inhibits breast cancer cell growth. Adamts17 expression can rapidly be induced by estrogens. siRNA knockdown of Sp1 or Myc demonstrated that Sp1 is required to induce Adamts17 gene expression in response to estrogen. Moreover, reporter assays showed that the proximal promoter and the upstream sequences were not capable of conferring estrogen responsiveness, suggesting that Sp1 elements may be located in the downstream intronic region. We further demonstrated that Sp1 and Myc binding in the proximal promoter region contributed to the Adamts17 basal expression. Furthermore, histone deacetylase (HDAC) and methylase inhibitors also induced Adamts17 expression, indicating that epigenetic alterations, such as aberrant HDAC or/and methylation are associated with dysregulated Adamts17 expression. By meta-analysis using Oncomine microarray data, we found that higher Adamts17 expression is found in several human cancer cell subtypes, especially in breast ductal carcinoma. Moreover, we found that there is an inverse correlation between higher Adamts17 expression and patients' survival. Our study suggests that Adamts17 may support breast cancer cell growth and survival. © 2014 Wiley Periodicals, Inc.
    Journal of cellular biochemistry. 06/2014;
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    ABSTRACT: Purpose:We sought to determine the usefulness of fragile X mental retardation 1 (FMR1) carrier testing among young infertile women with or without signs of ovarian insufficiency as compared with fertile women.Methods:Three cohorts of women were recruited to determine the cytosine-guanine-guanine (CGG) repeats trinucleotide repeat length in the 5'-untranslated region of the FMR1 gene in lymphocyte DNA. A total of 199 fertile women, who were reported to have conceived within 3 months, were recruited together with 372 infertile women with ongoing menstrual cycles and 48 infertile women with primary ovarian insufficiency. The various ranges of FMR1 CGG repeat lengths among infertile women were compared with those of fertile controls. In infertile women with ongoing menstrual cycles, the serum concentrations of follicle-stimulating hormone, anti-Muellerian hormone, and inhibin B were measured during the early follicular phase.Results:None of the three categories of FMR1 CGG repeat length expansions (premutation, intermediate range, and high normal range) were more prevalent among infertile women than among fertile women. The CGG repeat length was not correlated with any of the ovarian reserve parameters.Conclusion:In comparison with a generalized preconception screening strategy, infertility as a criterion, even together with reduced ovarian reserve, is not suitable for identifying a higher proportion of women with expanded FMR1 CGG repeat length.Genet Med advance online publication 10 October 2013Genetics in Medicine (2013); doi:10.1038/gim.2013.146.
    Genetics in medicine: official journal of the American College of Medical Genetics 10/2013; · 3.92 Impact Factor
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    ABSTRACT: To study the distribution of a set of polymorphic alleles of genes encoding key regulators of the menstrual cycle in cohorts of women with different levels of fertility. Prospective cohort study. University hospital. Two hundred fertile women, who reported to have conceived within 3 months, 348 women with ongoing menstrual cycles suffering of infertility, and 48 infertile women diagnosed with infertility and premature ovarian failure (POF). Eleven polymorphisms of genes with known associations with surrogate parameters of female ovarian function were analyzed. The prevalence of polymorphic alleles in the three distinct cohorts after adjustment for age. The distributions of the allelic variants were compared with the fertility status of the recruited women. Using age-adjusted logistic regression analysis and the Bonferroni correction for multiple corrections, the CC-allele of the PvuII polymorphic variant in intron 1 of the ESR1 gene was twice as prevalent among women suffering from infertility. None of the other polymorphisms were distributed differently among the three cohorts. The ESR1-PvuII polymorphism emerges as a potential candidate for the early prediction of infertility due to premature ovarian aging.
    Fertility and sterility 06/2012; 98(4):965-972.e5. · 3.97 Impact Factor