Circulatory miRNA-155, miRNA-21 target PTEN expression and activity as a factor in breast cancer development

Abstract

Breast cancer is a complex disease with multiple factors involved in its pathophysiological development. genetic mutations of BRCA1, BRCA2 and p53 are among the most well-studied factors. The role of other genetic factors like altered expression profiles, SNPs in the regulatory regions of different genes or epigenetic factors like promoter methylation and histone modifications are also well studied but no solid understanding is available on distinct key players triggering malignancy in breast cancer, (Phosphatase and tensin homolog) PTEN is known to be a crucial tumor suppressor as it has been reported to be missing or abnormally expressed in many cancer cells. Here in this were studied how PTEN is expressed in malignant and benign cancer cells by investigating its expression profile and cellular location using Immuno-fluorescence microscopy. At the same time, quantitative studies of the circulatory mi-RNAs related to the downregulation of PTEN, namely mir-21 and mir-155 have studied also. Sixty biopsy samples, forty were diagnosed to be malignant and twenty were benign. It has been found that PTEN is normally expressed in benign samples and its normally localized in the cell membrane, while in malignant samples the expression level of PTEN is lower or absent and it is translocated to the cytoplasm. Interestingly the quantitative expression of circulatory mir-21 and mir-155 in the blood plasma of the corresponding patients showed a related pattern with higher expression in malignant samples, therefore can it's clear that PTEN is in the cross-talk of genetics and epigenetic regulation in regard of the development of malignant breast cancer. At the same time, this study confirms the importance of circulatory miRNAs as a biomarker for early breast cancer detection.