Arsenic induced Hippo pathway dysregulation linked to hTERT hypo-methylation in breast cancer patients

A key stage in the development of almost all types of malignancies is the dysregulation of telomeres and telomerase (hTERT). It has been suggested that arsenic-mediated changes in gene methylation status can mute tumor suppressor genes or increase oncogene expression, resulting in long-term alterations in the activity of genes governing cell transformation. Recent study demonstrated that, long-term exposure to an environmentally relevant dose of arsenic affects cellular development by interfering with the Hippo signaling system. The current study's objective is to ascertain the underlying molecular cause of arsenic induced telomerase alteration and how it is associated with gene methylation.

Twenty-eight female with intermittent breast cancer from arsenic exposed areas were selected, after surgery, a sample of the tumor and the healthy tissue (which serves as a control group) were extracted for further processing. Arsenic concentration was analyzed by atomic absorption spectrometry. Western blotting and RT-PCR were used to analyze the telomerase expression. Additionally, MS-PCR was used to identify the genetic and epigenetic changes, respectively.

According to our research, 65% of female breast cancer patients had extremely high arsenic concentrations with elevated telomerase expression. The cause of this up regulation of telomerase expression is hTERT promoter hypomethylation.

The findings also demonstrated a substantial association between breast cancer patients' upregulation of hTERT and their exposure to arsenic and fine-needle biopsy specimens may provide further predictive information. Higher telomerase expression was associated with a worse outcome.