ABSTRACT
Previous studies have shown that excess arsenic (As) in the drinking water could cause various types of diseases (e.g. blackfoot disease, skin cancer, bladder cancer, etc.). According to a governmental survey, more than half a million residents in Taiwan had drinking water containing As levels higher than 0.05 mg/L, and therefore health effects of As in drinking water are important public health issues in Taiwan. The incidence, as well as mortality, in the blackfoot disease-endemic area of southwestern Taiwan is exceptionally high. However, the mechanism of bladder cancer from long term exposure to As through drinking water is still unknown. Some reports have demonstrated that As can disrupt mitosis and thus induce apoptosis and centrosome aneuploidy. Aneuploidy is a common phenomenon in cancer cells is regulated by Aurora A (STK15). Previous studies also showed that Aurora A was over-expressed in several types of human cancers and that polymorphisms of STK15 Phe31Ile in Aurora-A gene were associated with cancer risks. There is 59.4% of the bladder cancer specimens showed Aurora-A over-expression, and 45.5% of the patients were from the blackfoot disease endemic area. The tumor suppressor p53 Pro72Arg is an important regulator of the cell cycle and apoptosis that is frequently inactivated in human cancers. Furthermore, deletion of the p53 gene results in centrosome amplification that is reminiscent of one of the phenotypes induced by elevated expression of Aurora-A/STK15, suggesting a crosstalk between the two proteins.
