Exposure to pesticides increases levels of uPA and uPAR in pre-malignant human prostate cells

Pesticides are associated with prostate carcinogenesis and mortality; however, their exact mechanisms of action are poorly defined. We have used a transformed but non-tumorigenic human prostate epithelial line to determine the effect of common herbicides and insecticides on expression of urokinase and its receptor, uPAR. The herbicide Roundup and insecticides Lorsban and Warrior induced uPA while Lorsban and Warrior also induced uPAR. Furthermore, a combination of Roundup + Lorsban or Roundup + Warrior produced greater increases in uPA and uPAR than when agents were used alone. Both active and “inactive” chemicals within these pesticides are important for the effects observed as the neat chemicals alone failed to induce uPA and were less potent inducers of uPAR. Thus, specific pesticide formulations, especially when combined, can increase uPA and uPAR expression in vitro in transformed prostate epithelial cells.