Revista Europea de Biología Experimental Acceso abierto

Abstracto

Effect of dasatinib and herceptin on Her-2 gene transfection in ER/PR positive breast cancer cells

Alireza Akbari Khorram, Selvam Arjunan, Forough Jannesari and Radhakrishnan Senthilkumar

Major nuclear receptors, such as Estrogen (ER) and progesterone (PR) play a significant role in breast cancer biology. However, their role in developing chemoresistance in breast cancer has received less attention. The development of reliable gene expression arrays, real-time quantitative RT-PCR, and immunohistochemical techniques for studying ER/PR have revealed their potential role in developing chemoresistance. Advances in our understanding of both ER/PR functional networks and epidermal growth factor receptor (EGFR) signaling pathways have revealed a frequent interplay between ER/PR and EGFR in cell growth, which is clinically relevant to breast cancer. Understanding how EGFR and their downstream kinases are activated by ER/PR (and vice-versa) is a central goal for maximizing treatment opportunities in breast cancer. In order to understand the connection between nuclear receptor ER/PR function and EGFR-2 (Her-2) in chemoresistance/ chemosensitivity found in breast cancer biology, this study has modified the chemosensitivity of MCF-7 cells by transfecting MCF-7 cells with Her-2 gene in vitro. It showed that cancer cells were differentially sensitive to anticancer therapy (Herceptin with Dasatinib), compared to the untransfected cells. The wound healing assay that measures the invasion potential of cancer cells showed that transfection of Her-2 into MCF-7 cell appreciably increased its invasion property. This result confirms that Her-2 expression in breast cancer cells drives the metastasis of cancer cells outside its primary site.