SPROUTY-2 represses the epithelial phenotype of colon carcinoma cells via upregulation of ZEB1 mediated by ETS1 and miR-200/miR-150
SPROUTY-2 (SPRY2) is a modulator of tyrosine kinase receptor signaling with receptor- and cell type-dependent inhibitory or enhancing effects. Studies on the action of SPRY2 in major cancers are conflicting and its role remains unclear. Here we have dissected SPRY2 action in human colon cancer. Global transcriptomic analyses show that SPRY2 downregulates genes encoding tight junction proteins such as claudin-7 and occludin and other cell-to-cell and cell-to-matrix adhesion molecules in human SW480-ADH colon carcinoma cells. Moreover, SPRY2 represses LLGL2/HUGL2, PATJ1/INADL and ST14, main regulators of the polarized epithelial phenotype, and ESRP1, an epithelial-to-mesenchymal transition (EMT) inhibitor. A key action of SPRY2 is the upregulation of the major EMT inducer ZEB1, as these effects are reversed by ZEB1 knock-down by means of RNA interference. Consistently, we found an inverse correlation between the expression level of claudin-7 and those of SPRY2 and ZEB1 in human colon tumors. Mechanistically, ZEB1 upregulation by SPRY2 results from the combined induction of ETS1 transcription factor and the repression of microRNAs (miR-200 family, miR-150) that target ZEB1 RNA. Moreover, SPRY2 increased AKT activation by epidermal growth factor, whereas AKT and also Src inhibition reduced the induction of ZEB1. Altogether, these data suggest that AKT and Src are implicated in SPRY2 action. Collectively, these results show a tumorigenic role of SPRY2 in colon cancer that is based on the dysregulation of tight junction and epithelial polarity master genes via upregulation of ZEB1. The dissection of the mechanism of action of SPRY2 in colon cancer cells is important to understand the upregulation of this gene in a subset of patients with this neoplasia that have poor prognosis.Oncogene advance online publication, 12 October 2015; doi:10.1038/onc.2015.366.
Access to sterile syringes by injection drug users in Puerto Rico [Meeting Abstract]
A variety of studies have concluded that a primary reason injection drug users (IDUs), their sexual partners, and children continue to be: infected with HIV is the lack of access to sterile syringes. The present study employed ethnographic interviews and observations to examine access to sterile syringes by IDUs in Puerto Rico between July 1995 and June 1997, a time characterized by the absence of legal restrictions on the sale and possession of syringes and the presence of a government-sponsored ner:needle exchange program. Sources of sterile syringes identified by severely addicted drug injectors in two metropolitan San Juan communities are described and compared, and the reasons IDUs access one source rather than another are explored. Detailed descriptions of sources of syringes and syringe acquisition provide a basis for discussing: 1) challenges that confront the needle exchange program, and 2) the potential use of private syringe sellers and pharmacies to increase IDUs access to sterile syringes, referrals to social and medical services, and information about blood-borne pathogens (including HIV) and hygienic injection practices.
Essix appliances. Provisional anterior prosthesis for pre and post implant patients
Missing anterior teeth are being replaced by implant-supported restorations quite frequently in modern dentistry. Providing the patient with a temporary prosthesis prior to or following implant fixture placement must satisfy established esthetic and functional criteria. When orthodontic treatment is included as part of the overall treatment effort, additional considerations include the retention and stabilization of newly established tooth positions. This article describes the fabrication, use and advantages of a provisional anterior prosthesis that replaces missing teeth prior to or following implant placement