Arsenic-induced c-Src activation in uroepithelium.
Simeonova-PP; Wang-S; Hulderman-T; McKinstry-M; Luster-M
FASEB J 2002 Mar 16(5):A902
Environmental or occupational exposure to arsenic is associated with a greatly increased risk of skin, urinary bladder and respiratory tract cancers in arseniasis-endemic areas throughout the world. Arsenic shares many properties of tumor promoters by affecting specific cell signal transduction pathways responsible for cell proliferation. In the current studies, we demonstrate that arsenic activates c-Src in a human uroepithelial cell line. Using pharmacological and genetic inhibition of Src, we found that c-Src activity is a prerequisite for arsenic-induced EGFR and ERK activation in these cells. Consistent with these in vitro observations, exposure of mice to arsenic in drinking water, which has been found previously to be associated with AP-I activation and epithelial proliferation, induces interaction of EGFR and c-Src in the urinary bladder. This response is also accompanied with an increase in ERK activation. The findings represent a potential pathway for mediating arsenic-induced phenotypic changes in the uroepithelium.
Arsenic-compounds; Occupational-exposure; Environmental-exposure; Skin-cancer; Bladder-cancer; Respiratory-system-disorders; Cell-damage; Tumors; In-vitro-studies; Urogenital-system-disorders
NIOSH, 1095 Willowdale Road, Morgantown, WV 26505
Abstract; Conference/Symposia Proceedings
Disease and Injury; Asthma and Chronic Obstructive Pulmonary Disease; Research Tools and Approaches; Cancer Research Methods
The FASEB Journal, Experimental Biology 2002, New Orleans, Louisiana, April 20-24, 2002