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Minerva Biotecnologica 2018 June;30(2):45-50

DOI: 10.23736/S1120-4826.17.02348-5

Copyright © 2017 EDIZIONI MINERVA MEDICA

lingua: Inglese

Suicide gene therapy for breast cancer with a suicide-inducing vector carrying the mammaglobin-1 promoter

Ali GHANBARIASAD 1, 2, Mojgan BANDEHPOUR 2, 3, 4, Hajar YAGHOOBI 5, Bahram KAZEMI 3, 4

1 Department of Medical Biotechnology, School of Medicine, Fasa University of Medical Sciences, Fasa, Iran; 2 Department of Medical Biotechnology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 3 Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 4 Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 5 Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran


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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.
RESULTS: 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.


KEY WORDS: BAX protein, human - Genetic therapy - Neoplasms - Mammaglobin A

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