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. <br />.

Keywords: AKT/mTOR signaling pathway components; Prostate Cancer; benign prostatic hyperplasia; progesterone receptor (PR); transcription and growth factors.

Figure 1

Progesterone Receptor (PR) Expression in BH and PCa Tissues. Note: PR expression was enhanced in PCa tissues compared to BH ones. The significance of PR in prostate cells remains unknown. It is shown PR is involved in a large number of alternative, non-genomic signaling cascades, growth factors activation that results in cancer biology change

Figure 2

The Protein Level of Nuclear Factors Brn-3α, TRIM16 in BH, and PCa Tissues in Patients with PR Expression <0.01 RLU and >0.01RLU. Note: A - Western blot of transcription factors Brn-3α, TRIM16; 1, 3 - tumor tissue; 2, 4 - normal tissue; B - the content of transcription factors Brn-3α, TRIM16 in the prostate tissue of patients with BH and prostate cancer with PR expression less than 1.0 RLU (<1 RLU.) and higher than 1.0 RLU (> 1 RLU.). Regulatory peptides are shown to be promising factors, which can regulate the transcriptional activity of both AR and ER and can be implicated in hormonal oncogenesis. The revealed data indicated no changes in Brn-3α and TRIM16 protein levels in PCa and BH patients. The significant results were obtained in the study of their mRNA rate