Suicide Gene Therapy for Breast Cancer With a Suicide-Inducing Vector Carrying the Mammaglobin-1 Promoter Publisher



Ghanbariasad A^{1, 2} ; Bandehpour M^{2, 3, 4} ; Yaghoobi H⁵ ; Kazemi B^{3, 4}
Source: Minerva Biotecnologica Published:2018

Abstract

BACKGROUND: Breast carcinoma is the most frequent cancer among women and finding a therapeutic approach is necessary for the treatment of this carcinoma. Gene therapy is a promising therapeutic approach for cancer. Targeted expression of the desired therapeutic proteins within the tumor cells is the best approach to reduce toxicity and improve survival. The mammaglobin-1 gene encodes a novel, breast cancer-associated glycoprotein. Mammaglobin-1 expression is restricted to the mammary gland and the function of the mammaglobin-1 protein is unknown. No mammaglobin-1 expression has been reported in various types of benign tissue or neoplasia other than the breast carcinomas. Over expression of mammaglobin-1 gene was reported in breast cancer tissues by some scientists. In this study, for the first time, the mammaglobin-1 promoter was introduced as a cancer specific promoter with a high efficacy. METHODS: A suicide-inducing vector that expresses the BAX suicide gene under the transcriptional control of the mammaglobin-1 promoter was constructed and evaluated against breast cancer in vitro. RESULT S: These data show that the mammaglobin-1 promoter is active in the breast cancer cell lines. Under the control of the mammaglobin-1 promoter, BAX expression in MD-MBA 438 cell line was five-fold higher than in human embryonic kidney (HEK) cell line and no expression was found in A549 cell line. With the help of mammaglobin-1 promoter, a wonderful enhancement was observed in the apoptosis in breast cancer cell lines. CONCLUSIONS: Concerning the expression of BAX gene under the control of mammaglobin-1, it can be used to specify suicide gene therapy in the treatment of breast tumor. © 2017 EDIZIONI MINERVA MEDICA.