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Overexpression of cell surface glycoproteins of the CD44 family is an early event in the colorectal adenoma-carcinoma sequence. This suggests a link with disruption of APC tumor suppressor protein-mediated regulation of beta-catenin/Tcf-4 signaling, which is crucial in initiating tumorigenesis. To explore this hypothesis, we analyzed CD44 expression in the(More)
A remarkable feature of regenerative processes is their ability to halt proliferation once an organ's structure has been restored. The Wnt signalling pathway is the major driving force for homeostatic self-renewal and regeneration in the mammalian intestine. However, the mechanisms that counterbalance Wnt-driven proliferation are poorly understood. Here we(More)
Two forms of genetic instability have been described in colorectal cancer: microsatellite instability and chromosomal instability. Microsatellite instability results from mutations in mismatch repair genes; chromosomal instability is the hallmark of many colorectal cancers, although it is not completely understood at the molecular level. As truncations of(More)
Colorectal cancer arises through a gradual series of histological changes, each of which is accompanied by a specific genetic alteration. In general, an intestinal cell needs to comply with two essential requirements to develop into a cancer: it must acquire selective advantage to allow for the initial clonal expansion, and genetic instability to allow for(More)
Mutations in the APC gene are responsible for familial adenomatous polyposis (FAP) and for the majority of sporadic colorectal cancers. The establishment of genotype-phenotype correlations in FAP is often complicated by the great clinical variability observed among carriers of the same APC mutation even within the same kindred. This variability is likely to(More)
BACKGROUND & AIMS Synchronous activation of the Wnt signaling pathway, mostly because of loss of function of the APC tumor suppressor, and of the oncogenic KRAS-signaling pathway is very frequent in colorectal cancer and is associated with poor prognosis. METHODS We have generated a compound transgenic mouse model, KRAS(V12G)/Apc(+/1638N), to recapitulate(More)
The Wnt signal-transduction pathway induces the nuclear translocation of membrane-bound beta-catenin (Catnb) and has a key role in cell-fate determination. Tight somatic regulation of this signal is essential, as uncontrolled nuclear accumulation of beta-catenin can cause developmental defects and tumorigenesis in the adult organism. The adenomatous(More)
According to the classical interpretation of Knudson's 'two-hit' hypothesis for tumorigenesis, the two 'hits' are independent mutation events, the end result of which is loss of a tumor suppressing function. Recently, it has been shown that the APC (adenomatous polyposis coli) gene does not entirely follow this model. Both the position and type of the(More)
In this paper, we describe the detailed analysis of about 75 kb of genomic DNA flanking the 5' end of the mouse alpha-globin region and complete the transcription map of the human region. Previously, we established the homology of the human and mouse alpha-globin upstream flanking regions (alpha UFR) and characterized in detail the mouse alpha-globin major(More)
The human alpha-globin gene cluster (30 kb) is embedded in a GC-rich isochore very close to the telomere of Chromosome (Chr) 16p. The alpha-Locus Controlling Region (alpha-LCR) is located upstream of the adult alpha-globin genes and has been shown to be essential for their expression. In this study we have been looking for expressed genes in the region(More)