Association between YAP expression in neoplastic and non‐neoplastic breast tissue with arsenic urinary levels

• Published in: Journal of applied toxicology 2017-10, Vol.37 (10), p.1195-1202
• Main Authors: Michel‐Ramirez, Gladis, Recio‐Vega, Rogelio, Ocampo‐Gomez, Guadalupe, Palacios‐Sanchez, Eduardo, Delgado‐Macias, Manuel, Delgado‐Gaona, Manuel, Lantz, Robert Clark, Gandolfi, Jay, Gonzalez‐Cortes, Tania
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; Adult; Anthropometry; Apoptosis; Arsenic; Arsenic - toxicity; Arsenic - urine; Breast - drug effects; Breast - metabolism; Breast cancer; Breast Neoplasms - chemically induced; Breast Neoplasms - genetics; Cancer; Cell growth; Cell Line, Tumor; Cell Nucleus - drug effects; Cell Nucleus - metabolism; Cell proliferation; Cell Proliferation - drug effects; Critical components; Cross-Sectional Studies; Cytoplasm; Cytoplasm - metabolism; Drinking water; Exposure; Female; Genomic instability; Health risks; Humans; Immunohistochemistry; Life Style; Middle Aged; Nuclei; Oxidative stress; Pathogenesis; Phosphoproteins - genetics; Phosphoproteins - metabolism; Proteins; Socioeconomic Factors; Stability; Staining; Surveys and Questionnaires; Transcription Factors; Tumor suppressor genes; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism; Urine; Xenobiotics; YAP; Yes Associated Protein
• ISSN: 0260-437X; 1099-1263
• DOI: 10.1002/jat.3481

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. Yes‐associated protein (YAP) 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 by different xenobiotics, including arsenic. 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 arsenic 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. The results disclosed a significant lower percentage of cytoplasm YAP expression in cases and that YAP high‐intensity staining in the cytoplasm but not in the nucleus decreases the risk for breast cancer. In conclusion, our overall data suggest that YAP may act as a tumor suppressor protein because their reduced expression in cases, which can induce an environment favorable for inhibition of apoptosis and promoting cellular proliferation by increasing genetic instability of cells, which might contribute to the pathogenesis of cancer. Copyright © 2017 John Wiley & Sons, Ltd. YAP expression can contribute to a malignant cellular phenotype acting as a tumor suppressor or oncogene. The study assessed and compared the expression of YAP by immunohistochemistry in neoplastic and non‐neoplastic breast tissue from women chronically exposed to As. The results disclosed a significant lower percentage of cytoplasm YAP expression in cases, and that YAP high intensity staining in the cytoplasm decreases the risk for breast cancer. The overall data suggest that YAP may acts as a tumor suppressor protein.