Abstract
Cancer of the breast is the most common form of malignant disease occurring among women of the western world and environmental substances seem to be involved in the etiology of this disease. Many studies have found an association between human cancer and exposure to agricultural pesticides and among them parathion, the organophosphorous pesticide used in agriculture to control mosquito plagues. The association between breast cancer and prolonged exposure to estrogens suggests that this hormone also may have a role in such process. However, the causative factors for breast carcinogenesis remain an enigma. The objective of this study was to determine the effects of 17beta-estradiol (E2) and parathion on cell transformation of human breast epithelial cells in vitro. The results of this study showed that parathion alone and in combination with E2 induced malignant transformation of an immortalized human breast epithelial cell line, MCF-10F, and the malignant feature was confirmed by anchorage independency and invasive capabilities. Parathion alone efficiently elevated the expression of EGFR, c-Kit, Trio, Rac 3, Rho-A, and mutant p53 proteins. Analysis of gene expression using commercially available human cell cycle array revealed transcriptional alterations in 22 out of a total of 96 genes. Among them, nine genes involved in the regulation of cell cycle were altered. These included cyclins (A1, A2, C, G1, G2, and H), cyclin-dependent kinases (CDKs), and minichromosome maintenance deficient (MCM). Results suggest that parathion has the potency to cause malignant transformation of breast epithelial cells through modulation of expression of cell cycle regulated genes.