Abstract

Breast cancer research has developed rapidly in the past few decades, leading to longer survival times for patients and opening up the possibility of developing curative treatments for advanced breast cancer. Our increasing knowledge of the biological pathways associated with the progression and development of breast cancer, alongside the failure of conventional treatments, has prompted us to explore gene therapy as an alternative therapeutic strategy. We previously reported that gef gene from E. coli has shown considerable cytotoxic effects in breast cancer cells. However, its action mechanism has not been elucidated. Indirect immunofluorescence technique using flow cytometry and immunocytochemical analysis were used to detect breast cancer markers: estrogen (ER) and progesterone (PR) hormonal receptors, human epidermal growth factor receptor-2 proto-oncogene (c-erbB-2), ki-67 antigen and p53 protein. gef gene induces an increase in ER and PR expressions and a decrease in ki-67 and c-erbB-2 gene expressions, indicating a better prognosis and response to treatment and a longer disease-free interval and survival. It also increased p53 expression, suggesting that gef-induced apoptosis is regulated by a p53-mediated signaling pathway. These findings support the hypothesis that the gef gene offers a new approach to gene therapy in breast cancer.

Highlights

  • Breast cancer is the most common malignant tumor and the highest cause of death by neoplasia among women [1]

  • Using the MCF-7 breast cancer cell line, we developed a new MCF-7 cell line transfected with a mammalian expression vector containing the gef gene (MCF-7TG) under control of the mouse mammary tumor virus (MMTV) promoter

  • The present study was designed to determine the mechanisms underlying the considerable cytotoxic effects of the gef gene in breast cancer cells, exploring the apoptosis pathway and the ability of the gef gene to affect the degree of maturation in breast cancer cells by studying its effects on a panel of specific breast tumor markers

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Summary

Introduction

Breast cancer is the most common malignant tumor and the highest cause of death by neoplasia among women [1] It is correlated with multiple histopathological forms, growth rates, variations in metastatic capacity and responses to hormonal therapy. Gef gene induces an increase in ER and PR expressions and a decrease in Ki-67 and c-erbB-2 gene expressions, indicating a better prognosis and response to treatment and a longer disease-free interval and survival. It increased p53 expression, suggesting that gef-induced apoptosis is regulated by a p53-mediated signaling pathway. These findings support the hypothesis that the gef gene offers a new approach to gene therapy in breast cancer

Results and Discussion
Immunocytochemical Analysis
Indirect Immunofluorescence Analysis
Cell Lines and Culture Conditions
Statistical Analysis
Conclusions
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