YAP expression in neoplastic and non-neoplastic breast tissue of women chronically exposed to Arsenic

The Hippo pathway regulates cell proliferation and apoptosis and it has been noted that loss of critical components of this pathway can lead to uncontrolled cell growth. Yap protein is an important component of this HIPPO pathway because YAP is the nuclear effector of the Hippo tumor suppressor pathway and it is crucial for the response to oxidative stress induced by cellular process and for different xenobiotics including arsenic (As). It has been proposed that YAP dysregulation can contribute to a malignant cellular phenotype acting as both a tumor suppressor and an oncogene. The aim of the study was to assess and compare the expression of YAP in neoplastic and non-neoplastic breast tissue of women chronically exposed to As through drinking water. YAP expression was assessed by immunohistochemistry in 120 breast biopsies from women with breast cancer and from women with other non-neoplastic breast pathologies. Arsenic concentration was quantified in urine and toenails. The results disclosed a lower percentage of YAP expression in the nucleus and in the cytoplasm in cases when compared to the registered in controls. High As levels decreases mainly YAP expression at the nucleus. YAP high intensity staining decreases the risk for breast cancer. The overall data suggest that YAP may acts as a tumor suppressor protein and that As is able to reduce the YAP translocation from the cytoplasm to the nucleus which can induce an environment favorable for inhibition of apoptosis and promoting cellular proliferation by increasing the genomic instability of cells.