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Increased phosphorylation of Akt in triple-negative breast cancers
Shinobu Umemura1, Sei Yoshida, Yoshikazu Ohta
1Department of Pathology, Tokai University School of Medicine, Isehara, Kanagawa 259-1193, Japan. umemura@is.icc.u-tokai.ac.jp
Abstract:
Cells from breast cancers lacking hormone receptors (estrogen receptor [ER], progesterone receptor [PgR]) and human epidermal growth factor receptor (HER) 2 strongly express the cell proliferation marker Ki-67. However, the mechanisms of and stimulus signals involved in cell proliferation of this type of breast cancer are not well understood. The aim of the present study was to examine the characteristics of signal transduction in triple-negative (ER-, PgR-, and HER2-negative) breast cancers. For 44 tumor samples, western blotting analysis was conducted to examine the phosphorylation of HER2, external signal-regulated kinase (ERK)1 and -2 and Akt, and the immunohistochemical phenotypes of the samples with respect to ER and HER2 were also assessed. Phosphorylation of HER2 was detected in 4 of 15 immunohistochemically HER2-positive tumor samples (26.7%). ERK1/2 was more highly phosphorylated in triple-negative breast cancers. Phosphorylation of Akt kinase was significantly higher in triple-negative breast cancers. Triple-negative breast cancers are characterized by increased phosphorylation of Akt kinase. In the present study, we found for the first time that there is a population with a significantly activated Akt pathway in this type of breast cancer.
Insights
Triple-negative breast cancers show high cell proliferation. This study found significantly increased Akt pathway activation in these cancers, offering new insights into their growth mechanisms.
Area of Science:
- Oncology
- Molecular Biology
- Cell Signaling
Background:
- Triple-negative breast cancers (TNBC) lack estrogen receptors (ER), progesterone receptors (PgR), and HER2, yet exhibit high cell proliferation.
- The underlying mechanisms and signaling pathways driving TNBC proliferation remain poorly understood.
Purpose of the Study:
- To investigate the signal transduction characteristics in triple-negative breast cancers.
- To identify key molecular pathways involved in TNBC growth.
Main Methods:
- Western blotting was used to analyze protein phosphorylation in 44 TNBC tumor samples.
- Examined phosphorylation of HER2, ERK1/2, and Akt.
- Immunohistochemical analysis assessed ER and HER2 phenotypes.
Main Results:
- HER2 phosphorylation was observed in 26.7% of HER2-positive samples.
- Elevated ERK1/2 phosphorylation was detected in triple-negative breast cancers.
- Significantly higher Akt kinase phosphorylation was a key characteristic of TNBCs.
Conclusions:
- Triple-negative breast cancers exhibit increased Akt kinase phosphorylation.
- A subset of TNBCs demonstrates a significantly activated Akt pathway, representing a novel finding.
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