Browsing by Subject "Gene regulation"

Now showing 1 - 2 of 2
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    Modulation of EGFR gene transcription by secondary structures, a polymorphic repetitive sequence and mutations - a link between genetics and epigenetics
    (F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2000) Gebhardt, F.; Bürger, H.; Brandt, B.
    The epidermal growth factor receptor (EGFR) plays a crucial role in growth, differentiation and motility of normal as well as tumor cells. The transduction of extracellular signals to the cytoplasm via the receptor not only depends on ligand binding, but is also determined by the receptor density on the cell surface. Therefore , in terms of cancer diagnosis and therapeutic approaches targeting EGFR it is decisive to know how the expression level of EGFR is controlled. We found that transcription activity declines with increasing numbers of CA dinucleotides of a highly polymorphic CA repeat in the first intron epidermal growth factor receptor gene. In vivo data from cultured cell lines support these findings, although other regulation mechanisms can compensate this effect. In addition, we showed that RNA elongation terminates at a site closely downstream of the simple sequence repeat (SSR) and that there are two separate major transcription start sites. Model calculations for the helical DNA conformation revealed a high bend ability in the EGFR polymorphic region, es pecially if the CA stretch is extended. These data suggest that the CA-SSR can act like a joint bringing the promoter in proximity to a putative repressor protein bound downstream of the CASSR. The data suggest that this polymorphism is a marker for cancer linking genetic and epigenetic risk. Furthermore in breast cancer, heterozygous tumours with short CA-SSR showed an elevated EGFR-expression in contrast to tumours with longer CA-SSR. Tumours with loss of heterozygosity in intron 1 of egfr revealed an increased EGFR expression if the longer allele was lost. Moreover, deceased egfr gene dosages were significantly correlated to poor prognosis in breast cancer.
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    NF - KB function in the human myometrium during pregnancy and parturition
    (Murcia : F. Hernández, 2010) Cookson, Victoria J.; Chapman, Robert
    Interactions between the nuclear factor kappaB (NF-κB) family of proteins (RelA, RelB, c-Rel, p50 and p52) and DNA are vital for cells to function normally; for example, in the human myometrium, NF- κB-regulated pro-inflammatory mediators, including TNFα, IL-1ß, IL-8 and COX-2 are associated with the onset of labour. NF-κB, however, regulates the expression of over 400 genes, although it is unlikely these would all be activated in concert by a single inducer. At present, defining the role of the NF-κB RelA:p50 dimer, which governs a number of inflammatory promoters, is at the forefront of the parturition research field. However, to over-look the function of other family members and how they may regulate alternative signalling networks within reproductive tissues, only serves to ensure we will never fully understand the molecular circuitry influenced by this family of transcription factors. Consequently this review highlights other mechanisms by which the NF- κB family of regulators have been shown to function in other systems and how they may readily translate to understanding the regulation underpinning human parturition.