Domińska Kamila, Kowalska Karolina, Matysiak Zuzanna Elżbieta, Płuciennik Elżbieta, Ochędalski Tomasz, Piastowska-Ciesielska Agnieszka Wanda
Department of Comparative Endocrinology, Medical University of Lodz, Lodz 90‑752, Poland.
Department of Molecular Carcinogenesis, Medical University of Lodz, Lodz 90‑752, Poland.
Mol Med Rep. 2017 Jun;15(6):4352-4359. doi: 10.3892/mmr.2017.6514. Epub 2017 Apr 26.
An increasing number of researchers are focusing on the influence of local peptide hormones such as angiotensin II (Ang II) and relaxin 2 (RLN2) in the regulation of inflammation and carcinogenesis. The interaction between the renin‑angiotensin system (RAS) and relaxin family peptide system (RFPS) is known to influence the proliferation, adhesion and migration of normal and cancer prostate cell lines. The aim of the present study was to evaluate changes in the expression of nuclear factor‑κB subunit 1 (NFKB1), nuclear factor‑κB subunit 2 (NFKB2), REL proto‑oncogene nuclear factor‑κB p65 subunit (REL), RELA proto‑oncogene nuclear factor‑κB subunit (RELA) and RELB proto‑oncogene nuclear factor‑κB subunit (RELB) mRNA caused by Ang II and RLN2. The members of NF‑kB family are involved in many processes associated with cancer development and metastasis. Reverse transcription‑quantitative polymerase chain reaction analysis identified that both peptide hormones have an influence on the relative expression of nuclear factor‑κB. Following treatment with either peptide, NFKB1 expression was downregulated in all prostate cancer cell lines (LNCaP, DU‑145 and PC3), but not in normal epithelial cells (PNT1A). Conversely, RELB mRNA was enhanced only in non‑cancerous prostate cells. RELA expression was strongly stimulated in the most aggressive cell line, whereas REL mRNA was unchanged. In many cases, the effect was strictly dependent on the cell line and/or the type of peptide: Ang II increased expression of both RELA and REL genes in the androgen‑dependent cell line while RLN2 enhanced NFKB2 and RELA mRNA in androgen‑independent cells (DU‑145). Further research is needed to understand the regulation of NF‑κB family members by key renin‑angiotensin system and RFPS peptides in prostate cancer cells; however, prostate carcinogenesis appears to be influenced by the balance between the cross‑regulation of nuclear factor‑κB (NF‑κB) and androgen receptor pathways by Ang II and relaxin 2.
越来越多的研究人员关注局部肽类激素如血管紧张素II（Ang II）和松弛素2（RLN2）在炎症调节和致癌作用中的影响。已知肾素-血管紧张素系统（RAS）和松弛素家族肽系统（RFPS）之间的相互作用会影响正常和癌性前列腺细胞系的增殖、黏附和迁移。本研究的目的是评估由Ang II和RLN2引起的核因子-κB亚基1（NFKB1）、核因子-κB亚基2（NFKB2）、REL原癌基因核因子-κB p65亚基（REL）、RELA原癌基因核因子-κB亚基（RELA）和RELB原癌基因核因子-κB亚基（RELB）mRNA表达的变化。NF-κB家族成员参与许多与癌症发展和转移相关的过程。逆转录-定量聚合酶链反应分析表明，这两种肽类激素均对核因子-κB的相对表达有影响。用任何一种肽处理后，所有前列腺癌细胞系（LNCaP、DU-145和PC3）中的NFKB1表达均下调，但正常上皮细胞（PNT1A）中未下调。相反，RELB mRNA仅在非癌性前列腺细胞中增强。RELA表达在侵袭性最强的细胞系中受到强烈刺激，而REL mRNA则未改变。在许多情况下，这种作用严格依赖于细胞系和/或肽的类型：Ang II增加雄激素依赖性细胞系中RELA和REL基因的表达，而RLN2增强雄激素非依赖性细胞（DU-145）中的NFKB2和RELA mRNA。需要进一步研究以了解关键的肾素-血管紧张素系统和RFPS肽对前列腺癌细胞中NF-κB家族成员的调节；然而，前列腺癌发生似乎受Ang II和松弛素2对核因子-κB（NF-κB）和雄激素受体途径的交叉调节平衡的影响。
