THE PHOSPHORYLATED AKT1 KINASE, VASCULAR ENDOTHELIAL GROWTH FACTOR AND ITS RECEPTORS: INTRATUMORAL CONTENT AND PROGNOSTIC SIGNIFICANCE IN BREAST CANCER PATIENTS

Introduction. PI3K/Akt signaling pathway is an important intracellular regulatory mechanism controlling cues of growth factors stimuli, apoptosis, proliferation, and cell motility. Deregulation of activity/expression of PI3K/Akt signaling pathway proteins determines the development of different types of cancers, and according to recent studies these proteins may become promising prognostic factors in various types of cancer. The aim of the study. The goal of this study is to assess potential prognostic value of activated (phosphorylated) Akt1 kinase (pAkt1) and Akt1- associated proteins – vascular endothelial growth factor (VEGF) and two types of its receptors (VEGFR1 and VEGFR2) in breast cancer (BC). Methods. Study group enclosed 46 stage I-IV breast cancer patients. pAkt1, VEGF, VEGFR1, and VEGFR2 levels in tumor lysates were determined with the use of standard ELISA kits (R&D; Cell Signaling Technology, USA). Results. Approximately in 50% of breast cancer patients pAkt1 in tumors was elevated if compared to histologically unchanged mammary gland tissues. In this tumor Akt1 activity increases at late stages of the disease and in large tumors. The level of such upstream Akt1 effectors as VEGF, VEGFR1, VEGFR2 were elevated in 73-85% of investigated tumors if compared to unchanged tissues. The 9-year’s survival analysis of breast cancer patients revealed that the most promising prognostic factors could be the level both of intratumoral pAkt1 and one of its effectors, VEGFR1. Conclusion. Tumor pAkt1 and its effector VEGFR1 content may be considered as potential prognostic factor in breast cancer patients.