P53 But Not Cyclin E Acts in A Negative Regulatory Loop to Control HER-2 Expression in MCF-7 Breast Carcinoma Cell Line

  • Hamed Montazeri Department of Molecular Biology, Pasteur Institute of Iran, Tehran, Iran.
  • Saeid Bouzari Mail 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.
Keywords:
Breast cancer, Cyclin E, HER-2/neu, p53

Abstract

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.

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How to Cite
1.
Montazeri H, Bouzari S, Azadmanesh K, Ostad SN, Ghahremani MH. P53 But Not Cyclin E Acts in A Negative Regulatory Loop to Control HER-2 Expression in MCF-7 Breast Carcinoma Cell Line. Acta Med Iran. 51(8):513-519.
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