Publications (2)5.44 Total impact
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ABSTRACT: Extramammary Paget's disease (EMPD) is a rare cutaneous malignant neoplasm. The genetic alterations underlying its pathogenesis have less been described. Therefore, we analyzed the possible mutations in the KRAS, HRAS, NRAS, BRAF, ARAF, RAF1, PIK3CA, AKT1, CTNNB1 and APC genes as well as methylation and expression of CDH1 in 144 EMPD cases and 42 matched normal skin tissues. A distinct mutation profile was identified in EMPDs with 27 (19%) cases mutant for RAS and RAF genes and 50 (35%) cases harboring oncogenic mutations in PIK3CA and AKT1. Moreover, a mutually exclusive pattern was observed in the genetic variants in these two signaling pathways. No mutation was detected in CTNNB1 and APC genes. High prevalence of low expression and hypermethylation of CDH1 gene was detected in 33 and 48% of the EMPD cases, respectively. Furthermore, PIK3CA and AKT1 mutations were significantly correlated with CDH1 hypermethylation which could explain why the majority of EMPD cases with mutant PIK3CA and AKT1 were invasive. Our study demonstrates that genetic variants associated with constitutive activation of RAS/RAF and PI3K/AKT pathways are involved in the pathogenesis of EMPD. This may represent novel therapeutic targets for this skin cancer.International Journal of Cancer 07/2012; · 5.44 Impact Factor
Article: Identification of a hemocyte membrane protein of the silkworm, Bombyx mori, which specifically binds to bacterial lipopolysaccharide[show abstract] [hide abstract]
ABSTRACT: An in vitro system with isolated hemocytes of the silkworm, Bombyx mori (B. mori) was developed to examine the induction mechanism of insect antibacterial proteins by bacterial lipopolysaccharide (LPS). The gene expression of B. mori cecropin B, a representative antibacterial protein, was triggered by LPS in this in vitro system. To identify LPS-binding site(s) of the hemocytes, the [125I]LPS binding assay to the hemocytes was performed in vitro. The amount of [125I]LPS bound to hemocytes increased proportionately with the increase of incubation time and LPS dose. The binding was strongly inhibited by excess unlabeled LPS or lipid A, indicating that the binding of [125I]LPS to hemocytes contains a highly specific reaction. Moreover, the specific binding could not be detected with Bm-N4 cells in which cecropin B gene expression was not induced by LPS, suggesting that the LPS binding is specific for LPS responsive cells. The LPS binding was fully sensitive to the proteinase K treatment of intact hemocytes, suggesting that a protein(s) located on the surface of hemocytes is involved in the LPS binding. Fluorescein isothiocyanate (FITC) conjugated-LPS binding assay demonstrated that this compound mainly binds to granular cells rather than other hemocytes under our assay conditions. Affinity-labeling with photoreactive-LPS allowed the identification of a 11 kDa LPS-binding protein in hemocytes, which might relate to the specific membrane receptor for LPS.Insect Biochemistry and Molecular Biology.