Increased phosphorylation of Akt in triple-negative breast cancers - PubMed (original) (raw)

Increased phosphorylation of Akt in triple-negative breast cancers

Shinobu Umemura et al. Cancer Sci. 2007 Dec.

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.

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Figures

Figure 1

Figure 1

Immunoblotting analysis for human epidermal growth factor receptor (HER) 2, external signal‐regulated kinase (ERK)1/2, and Akt kinases. (a) Protein extracts from 44 tumor samples were separated by sodium dodecylsulfate–polyacrylamide gel electrophoresis and immunoblotted using antibodies for phosphorylated and total HER2, ERK1/2, and Akt. M1, M2, and M3 are markers for protein extracts in graded concentrations. (b) Phosphorylated HER2, ERK1/2, and Akt were compared between ER‐, PgR‐, and HER2‐negative cancers (▪), and other types of breast cancers, including ER+ and HER2−, ER+ and HER2+, and ER− and HER2+ cancers (□). Asterisks indicate _P_‐value (0.0023 for the _t_‐test and 0.06 for the Mann–Whitney test). Error bars represent SD. (c) The ratios of phosphorylated and total HER2, ERK1/2, and Akt were also compared between triple‐negative breast cancers (▪) and others (□). Asterisks indicate _P_‐value (0.006 for the _t_‐test).

Figure 2

Figure 2

Immunohistochemical analysis for phosphorylated Akt. Immunohistochemical results were evaluated by a combination of immunohistochemical intensity and population. The population of carcinoma‐positive cells with strong (3+), medium (2+), or weak (1+) intensity, or negative cells, were estimated. (b) The results of immunoblotting and immunohistochemical analysis were in good correlation. Solid circles indicate ER−, and PgR− and human epidermal growth factor receptor (HER)2−, and open circles indicate other types of breast cancers, including ER+ and HER2−, ER+ and HER2+, and ER and HER2+.

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