Axl -Gas6 signaling counteracts adenovirus type 5 E1A-mediated cell growth suppression and proapoptotic activity

The adenovirus type 5 E1A (abbreviated E1A) has previously been known as an immortalization oncogene because E1A is required for transforming oncogenes, such as ras and E1B, to transform cells in primary cultures. However, E1A has also been shown to downregulate the overexpression of the Her-2/neu oncogene, resulting in suppression of transformation and tumorigenesis induced by that oncogene. In addition, E1A is able to promote apoptosis induced by anticancer drugs, irradiation, and serum deprivation. Many tyrosine kinases, such as the EGF receptor, Her-2/Neu, Src, and Axl are known to play a role in oncogenic signals in transformed cells. To study the mechanism underlying the E1A-mediated tumor-suppressing function, we exploited a modified tyrosine kinase profile assay (Proc. Natl. Acad. Sci, 93, 5958–5962, 1996) to identify potential tyrosine kinases regulated by E1A. RT-PCR products were synthesized with two degenerate primers derived from the conserved motifs of various tyrosine kinases. A tyrosine kinase downregulated by E1A was identified as Axl by analyzing the Alu I-digested RT-PCR products. We isolated the DNA fragment of interest, and found that E1A negatively regulated the expression of the transforming receptor tyrosine kinase Axl at the transcriptional level. To study whether downregulation of the Axl receptor is involved in E1A-mediated growth suppression, we transfected axl cDNA into E1A-expressing cells (ip1-E1A) to establish cells that overexpressed Axl (ip1-E1A-Axl). The Axl ligand Gas6 triggered a greater mitogenic effect in these ip1-E1A-Axl cells than in the control cells ip1-E1A and protected the Axl-expressing cells from serum deprivation-induced apoptosis. Further study showed that Akt is required for Axl-Gas6 signaling to prevent ip1-E1A-Axl cells from serum deprivation-induced apoptosis. These results indicate that downregulation of the Axl receptor by E1A is involved in E1A-mediated growth suppression and E1A-induced apoptosis, and thereby contributes to E1A's anti-tumor activities. ^

Population-based cross -sectional survey on intestinal helminth infections with a focus on taeniasis among residents of El Paso, Texas and Ciudad Juarez, Mexico

Few studies have been conducted on the epidemiology of enteric infectious diseases of public health importance in communities along the United States-Mexico border, and these studies typically focus on bacterial and viral diseases. The epidemiology of intestinal helminth infections along the border has not recently been explored, and there are no published reports for El Paso and Ciudad Juarez, both of which are high traffic urban areas along the Texas-Mexico border. The purpose of this research project was to conduct a cross-sectional epidemiologic survey for enteric helminths of medical importance along the Texas-Mexico border region of El Paso and Ciudad Juarez and to evaluate risk factors for exposure to these parasites. In addition, an emphasis was placed on the zoonotic tapeworm, Taenia solium. This tapeworm is especially important in this region because of the increasing incidence of neurocysticercosis, a severe disease spread by carriers of intestinal T. solium. Fecal samples were collected from individuals of all ages in a population-based cross-sectional household survey and evaluated for the presence of helminth parasites using fecal flotations. In addition, a Taenia coproantigen enzyme linked immunosorbent assay (ELISA) was performed on each stool sample to identify tapeworm carriers. A standardized questionnaire was administered to identify risk factors and routes of exposure for enteric helminth infections with additional questions to assess risk factors specific for taeniasis. The actual prevalence of taeniasis along the Texas-Mexico border was unknown, and this is the first population-based study performed in this region. Flotations were performed on 395 samples and four (1%) were positive for helminths including Ascaris, hookworms and Taenia species. Immunodiagnostic testing demonstrated a prevalence of 2.9% (11/378) for taeniasis. Based on the case definition, a 3% (12/395) prevalence of taeniasis was detected in this area. In addition, statistical analyses indicate that residents of El Paso are 8.5 times more likely to be a tapeworm carrier compared to residents of Juarez (PR=8.5, 95% CI=2.35, 30.81). This finding has important implications in terms of planning effective health education campaigns to decrease the prevalence of enteric helminths in populations along the Texas-Mexico border. ^