ACTIVITY AND FUNCTIONAL CHARACTERISTICS OF CYTOCHROME P450 IN TUMORS AND BREAST ADIPOSE TISSUE OF PATIENTS WITH BREAST CANCER
DOI:
https://doi.org/10.32471/oncology.2663-7928.t-21-4-2019-g.8345Keywords:
breast cancer, CYP 19А1, CYP 1А2, cytochrome P450, mammary adipose tissue, obesity, tumorsAbstract
Cytochrome P450 (CYP) is an oxygenase that is involved in the biosynthesis and metabolism of estrogens and in tumor response to anti-estrogen therapy, so determining the role of CYP in the etiopathogenesis of breast cancer (BC) is important information and to understand the mechanism of sensitivity. Aim: to investigate cytochrome P450 levels (in oxidized and low-spin states) and CYP 1A2, CYP 19A1 isoforms in BC and mammary adipose tumors (MAT) in patients with BC. Object and methods: 58 samples of tumor tissue and mammary adipose tissue (5 cm from tumor node) of patients with stage II–III breast cancer (37 and 21 patients respectively) with different body mass index (BMI) — ≤ 2 and ≥ 25 kg/m2 were studied. The levels of oxidized and low-spin cytochrome P450 and its CYP 19A1 isoforms were examined by electron paramagnetic resonance and spectrophotometrically. Immunoblotting was performed according to standard protocols with antibodies against CYP 1A2, CYP 19A1, GAPDH (Santa Cruz Biotechnology, Santa Cruz, CA). Results: high levels of cytochrome P450 (CYP 19A1 and CYP 1A2 isoforms) were detected in stage II and III BC tissue and MAT. It is established that the formation of the P450 complex (CYP 19A1) with androstenedione in MAT of patients with BC reveals intense EPR signals with g factors of 8.1 and 3.28, which may be a marker of the metabolic activity of the enzyme. The accumulation of adipose tissue alters the activity of cytochrome P450, especially its low-spinous form; the increase in levels of oxidized (g = 2.42) and low-spin (g = 2.25) forms of the enzyme correlates with an increase in IBM (≥ 25 kg/m2). Increased levels of CYP 1A2 in tissue and MAT have also been established, suggesting a possible effect of CYP 1A2 on the energy metabolism of BC cells. Conclusions: have found high levels of cytochrome P450 in tumors and MAT in patients with BC, which has potential application as a biomarker in decision-making on personalized hormone therapy regimens. Increased CYP 1A2 and CYP 19A1 activity in MAT may be a risk factor for progression of BC, especially in the presence of obesity and with increased duration of estrogen exposure.
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