The neu oncogene, characterized by Weinberg and colleagues, is a transforming gene found in ethylnitrosourea‐induced rat neuro/glioblastomas; its human proto‐oncogene homologue has been termed erbB2 or HER2 because of its close homology with the epidermal growth factor receptor (EGF‐R) gene (c‐erbB1). Expression of the rat neu oncogene is sufficient for transformation of mouse NIH 3T3 fibroblasts in culture and for the development of mammary carcinomas in transgenic mice, but the neu proto‐oncogene has not been associated with cell transformation. We constructed a vector for expression of a chimeric cDNA and hybrid protein consisting of the EGF‐R extracellular, transmembrane and protein kinase C‐substrate domains linked to the intracellular tyrosine kinase and carboxyl terminal domain of the rat neu cDNA. Upon transfection with the construct, NIH 3T3 cells gave rise to EGF‐R antigen‐positive cell clones with varying amounts of specific EGF binding. Immunofluorescence and immunoprecipitation using neu‐ and EGF‐receptor specific antibodies demonstrated a correctly oriented and positioned chimeric EGF‐R‐neu protein of the expected apparent mol. wt on the surface of these cells. EGF or TGF alpha induced tyrosine phosphorylation of the chimeric receptor protein, stimulated DNA synthesis of EGF‐R‐neu expressing cells and led to a transformed cell morphology and growth in soft agar. In contrast, the neu proto‐oncogene did not show kinase activity or transforming properties when expressed at similar levels in NIH 3T3 cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract. We have studied the ability of the neu tyrosine kinase to induce a signal for the activation of cell growth-regulated genes. Serum-starved NIH 3T3 cells expressing an epidermal growth factor receptor (EGF-R)/neu construct encoding a hybrid receptor protein were stimulated with EGF and the activation of the neu tyrosine kinase and stimulation of growth factor inducible genes were followed at the mRNA, protein, and activity levels, and compared to the corresponding responses in the neu proto-oncogene and oncogene expressing cells. Induction of the expression ofjun mRNAs was an immediate early effect of EGF stimulation, followed by a marked increase in the
Complicated skin and skin-structure infections (cSSSI) are a common reason for hospitalization and practically all new antimicrobial agents against Gram-positive bacteria are studied in cSSSI. The aim of this population-based observational study was to assess the treatment of patients with cSSSI in areas with a low incidence of antibiotic resistance. The study population consisted of adult residents who were treated because of cSSSI during 2008-2011 from two Nordic cities, Helsinki and Gothenburg. In the final analysis population (460 patients; mean age 60.8 years; 60.9% male) 13.3% of patients had bacteraemia, 15.9% were admitted to an Intensive Care Unit and 51.5% underwent at least one surgical intervention. Treatment failure occurred in 28.2%, initial antibiotic treatment modification to another intravenous drug in 38.5% and streamlining in 5.0% of the cases. Gram-positive bacteria were predominantly isolated, with staphylococci (24.5%) and streptococci (16.0%) being the most common aetiologies. Median overall durations of hospital stay and antimicrobial treatment were 13 and 17 days, respectively, and on average 3.5 (SD 2.1) different antibiotics were used per patient. Oral antimicrobial treatment was continued in 64.3% of patients after discharge. The overall mortality rates in 30 days and in 12 months were 4.1% and 11.8%, respectively, and 16.4% of patients had a recurrence of SSSI within 12 months. In conclusion, in this population-based study antimicrobial treatment modifications were frequent and the treatment time was longer than recommended. However, bacteraemia, clinical failure and recurrences were more common than in previous non-population-based studies.
The MCF-7 cell line is a hormone-responsive human breast-cancer cell line, which has been extensively used in studies of estrogen regulation of cell growth. These studies have indicated that the growth stimulation of the MCF-7 cells by estrogens may be effected by an autocrine mechanism involving several growth factors, such as EGF, TGF alpha and IGF-I and their receptors. We have amplified and cloned tyrosine-kinase-related sequences from the MCF-7 cell mRNA using the polymerase chain reaction and characterized the partial cDNAs obtained by nucleic acid sequencing. Nine tyrosine kinase cDNAs and one serine/threonine kinase cDNA were identified among the amplified sequences. Four different tyrosine kinase genes encoding receptors for fibroblast growth factors (FGFs) were found to be expressed by the MCF-7 cells. In addition, differences were observed in the expression of these members of FGF receptor family in different breast-cancer cells. A putative tyrosine-kinase receptor and a novel serine/threonine kinase were preferentially expressed in estrogen-responsive tumor cell lines. However, no estrogen-dependent regulation of any of the novel tyrosine-kinase receptor mRNAs was found in any of the cell lines including the MCF-7 or ZR-75-I cells, where the expression of the neu proto-oncogene mRNA was decreased during estrogen treatment. The expression of several FGF receptors by breast-cancer cells suggests that FGFs may be involved in their growth regulation and tumorigenesis.
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