Progesterone Receptor Expression in the Benign Prostatic Hyperplasia and Prostate Cancer Tissues, Relation with Transcription, Growth Factors, Hormone Reception and Components of the AKT/mTOR Signaling Pathway

Abstract

Background: Progesterone receptor (PR) is a critical regulator in reproductive tissues that controls a variety of cellular processes. The objective of the study was to study the PR expression in patients with benign prostatic hyperplasia and prostate cancers in connection with the transcription, growth factors, AR, ERα, ERβ, and components of the AKT/ mTOR signaling pathway expression. Materials and methods: Ninety-seven patients with prostate pathology were enrolled in the study. Forty-two patients had benign prostatic hyperplasia (BH). Fifty-five patients had locally advanced prostate cancer (PCa). The PSA level and the amount of testosterone in the serum were measured using an ELISA assay. The expression level of NF-κB p65, NF-κB p50, HIF-1, HIF-2, growth factor VEGF, VEGFR2, CAIX, as well as AR, ERα, ERβ, PR, Brn-3α, TRIM16 were quantified by RT-PCR. The protein level of Brn-3α, TRIM16 was detected by Western Blotting. Results: Growth in PR expression was observed in PCa tissues compared to BH ones without changes in the clinical and pathological features of the patients. An increase in PR expression was detected in patients with PCa compared to BH. Its mRNA level depended on the expression of AR, Brn-3α, and TRIM16, components of the AKT/mTOR signaling pathway, transcription, and growth factors. An increase in the TRIM16 expression in the PCa tissues was noted in the case of a low PR level. We revealed the growth in PR expression was accompanied by the suppression of the signaling cascade activity, AR, Brn-3α mRNA level, and the enhanced PTEN expression in PCa tissues. The increase in PR expression in PCa led to a decrease in the level of mRNA of NF-κB, HIF-1, VEGF, and VEGFR2. Conclusion: In general, the data indicated the significance of the PR expression in the development of the prostate pathology that affected the cross-talk between the steroid hormone reception and signal transduction.

Cognitive enhancing effects of pazopanib in D‑galactose/ovariectomized Alzheimer’s rat model: insights into the role of RIPK1/RIPK3/MLKL necroptosis signaling pathway

“…Also, another study stated that pazopanib can halt rat liver fibrosis through modulating the pro-inflammatory cytokines TNF-α and IL-6 (Elshal et al 2015 ). Furthermore, a study conducted on patients with renal cell carcinoma revealed that pazopanib reduced the NF-κB p65 level in kidney cancer tissues (Spirina et al 2017 ). NF-κB activation triggers the transcription of β-secretase (Tamagno et al 2012 ) as well as several pro-inflammatory genes such as TNF-α (Lu et al 2010 ).…”

Progesterone and prostate: a history of scientific study and the modern view of the problem

“…При многофакторном анализе установлено, что экспрессия РП в опухолевых клетках была независимым негативным прогностическим фактором клинической неудачи лечения РПЖ [30,31]. 2020) обследовали 97 пациентов с опухолевой патологией предстательной железы (42 пациента с ДГПЖ, 55 пациентов с местно-распространенным РПЖ) на предмет оценки уровня экспрессии в клетках опухолевых тканей ядерных факторов NF-κB p65, NF-κB p50, HIF-1, HIF-2, факторов роста VEGF, VEGFR2, CAIX, сигнальных белков Brn-3α, TRIM16, а также андрогеновых рецепторов, ЭР-α, ЭР-β и РП [32]. Результаты показали более выраженную экспрессию РП у пациентов с РПЖ по сравнению с пациентами с ДГПЖ, а уровень его мРНК зависел от экспрессии андрогеновых рецепторов, сигнальных белков Brn-3α и TRIM16, компонентов сигнального пути AKT/mTOR и факторов роста.…”

“…Усиление экспрессии РП сопровождалось подавлением активности сигнального каскада андрогеновых рецепторов и уровней мРНК сигнального белка Brn-3α в опухолевых тканях, что сопровождалось снижением уровня экспрессии мРНК ядерных факторов NF-κB, HIF-1 и факторов роста VEGF и VEGFR2. Таким образом, полученные данные свидетельствуют о значимости экспрессии РП в развитии патологии предстательной железы [32].…”