Tehran University of Medical Sciences Acta Medica Iranica 0044-6025 51 8 2013 08 15 513 519 EN Hamed Montazeri Department of Molecular Biology, Pasteur Institute of Iran, Tehran, Iran. Saeid Bouzari Department of Molecular Biology, Pasteur Institute of Iran, Tehran, Iran. Kayhan Azadmanesh Department of Virology, Pasteur Institute of Iran, Tehran, Iran. Seyed Nasser Ostad Department of Toxicology Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. Mohammad Hossein Ghahremani Department of Toxicology-Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. AND Department of Molecular Medicine, School of Advanced Technology in Medicine, Tehran University of Medical Sciences, Tehran, Iran. 2015 10 11 Cyclin E, HER-2 and p53, are considered as major prognostic markers in breast cancer. As they are related in patho-clinical level, we aimed to check if they have any direct interaction on expression of each other. To study the effect of cyclin E on HER-2 expression, cell lines stably overexpressing cyclin E or its low molecular weight (LMW) isoforms were generated. To understand the results of p53 silencing either alone or in combination with cyclin E overexpression, we created three different p53 stably knocked down cell lines. Protein expression was analyzed by western blot, HER-2 expression in the established cell lines were determined using SYBR green real time PCR and data analyzed by REST software. Results indicate that HER-2 expression is only downregulated following p53 silencing and none of cyclin E isoforms can alter its expression. The presence of cyclin E isoforms in p53 silenced clones also does not altered HER-2 expression. Given the fact that p53 degradation is increased by HER-2 overexpression, these data can draw a regulatory loop in which a non-mutated functional p53 and HER-2 can bidirectionally regulate the expression of these two genes. This study improves our understandings of these pathways and these proteins can be introduced either as a marker or as a target in cancer treatment. https://acta.tums.ac.ir/index.php/acta/article/view/4400 https://acta.tums.ac.ir/index.php/acta/article/download/4400/4259