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gef Gene Expression in MCF-7 Breast Cancer Cells is Associated with a Better Prognosis and Induction of Apoptosis by p53-Mediated Signaling Pathway
Basic Cardiovascular Research Section, Department of Anatomy and Human Embriology, School of Medicine, University of Granada, Granada E-18012, Spain
Biopathology and Medicine Regenerative Institute (IBIMER), Granada 18100, Spain
Department of Health Sciences, University of Jaén, E-23071 Jaén, Spain
* Authors to whom correspondence should be addressed.
Received: 26 September 2011; in revised form: 20 October 2011 / Accepted: 26 October 2011 / Published: 31 October 2011
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.
Keywords: breast cancer; gef gene; tumor markers; loss of tumor malignancy
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Boulaiz, H.; Álvarez, P.J.; Prados, J.; Marchal, J.; Melguizo, C.; Carrillo, E.; Peran, M.; Rodríguez, F.; Ramírez, A.; Ortíz, R.; Aránega, A. gef Gene Expression in MCF-7 Breast Cancer Cells is Associated with a Better Prognosis and Induction of Apoptosis by p53-Mediated Signaling Pathway. Int. J. Mol. Sci. 2011, 12, 7445-7458.
Boulaiz H, Álvarez PJ, Prados J, Marchal J, Melguizo C, Carrillo E, Peran M, Rodríguez F, Ramírez A, Ortíz R, Aránega A. gef Gene Expression in MCF-7 Breast Cancer Cells is Associated with a Better Prognosis and Induction of Apoptosis by p53-Mediated Signaling Pathway. International Journal of Molecular Sciences. 2011; 12(11):7445-7458.
Boulaiz, Houria; Álvarez, Pablo J.; Prados, Jose; Marchal, Juan; Melguizo, Consolación; Carrillo, Esmeralda; Peran, Macarena; Rodríguez, Fernando; Ramírez, Alberto; Ortíz, Raúl; Aránega, Antonia. 2011. "gef Gene Expression in MCF-7 Breast Cancer Cells is Associated with a Better Prognosis and Induction of Apoptosis by p53-Mediated Signaling Pathway." Int. J. Mol. Sci. 12, no. 11: 7445-7458.