Regulation of mRNA gene expression of members of the NF-κB transcription factor gene family by angiotensin II and relaxin 2 in normal and cancer prostate cell lines

Domińska,Kamila; Kowalska,Karolina; Matysiak,Zuzanna  Elżbieta; Płuciennik,Elżbieta; Ochędalski,Tomasz; Piastowska‑Ciesielska,Agnieszka  Wanda

doi:10.3892/mmr.2017.6514

Regulation of mRNA gene expression of members of the NF-κB transcription factor gene family by angiotensin II and relaxin 2 in normal and cancer prostate cell lines

Authors:
- Kamila Domińska
- Karolina Kowalska
- Zuzanna Elżbieta Matysiak
- Elżbieta Płuciennik
- Tomasz Ochędalski
- Agnieszka Wanda Piastowska‑Ciesielska
View Affiliations

Affiliations: Department of Comparative Endocrinology, Medical University of Lodz, Lodz 90‑752, Poland, Department of Molecular Carcinogenesis, Medical University of Lodz, Lodz 90‑752, Poland
Published online on: April 26, 2017 https://doi.org/10.3892/mmr.2017.6514
Pages: 4352-4359

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

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.

View Figures

View References

1	Domińska K: Relaxin 2-a pregnancy hormone involved in the process of carcinogenesis. Ginekol Pol. 84:126–130. 2013. View Article : Google Scholar
2	Domińska K and Lachowicz-Ochedalska A: The involvement of the renin-angiotensin system (RAS) in cancerogenesis. Postepy Biochem. 54:294–300. 2008.(In Polish).
3	Wegman-Ostrosky T, Soto-Reyes E, Vidal-Millán S and Sánchez-Corona J: The renin-angiotensin system meets the hallmarks of cancer. J Renin angiotensin Aldosterone Syst. 16:227–233. 2015. View Article : Google Scholar
4	Nair VB, Samuel CS, Separovic F, Hossain MA and Wade JD: Human relaxin-2: Historical perspectives and role in cancer biology. Amino Acids. 43:1131–1140. 2012. View Article : Google Scholar
5	Domińska K, Ochędalski T, Kowalska K, Matysiak-Burzyńska ZE, Płuciennik E and Piastowska-Ciesielska AW: A common effect of angiotensin II and relaxin 2 on the PNT1A normal prostate epithelial cell line. J Physiol Biochem. 72:381–392. 2016. View Article : Google Scholar
6	Domińska K, Ochędalski T, Kowalska K, Matysiak-Burzyńska ZE, Płuciennik E and Piastowska-Ciesielska AW: Interaction between angiotensin II and relaxin 2 in the progress of growth and spread of prostate cancer cells. Int J Oncol. 48:2619–2628. 2016.
7	Jin R, Sterling JA, Edwards JR, DeGraff DJ, Lee C, Park SI and Matusik RJ: Activation of NF-kappa B signaling promotes growth of prostate cancer cells in bone. PLoS One. 8:e609832013. View Article : Google Scholar :
8	Hoesel B and Schmid JA: The complexity of NF-κB signaling in inflammation and cancer. Mol Cancer. 12:862013. View Article : Google Scholar :
9	Nguyen DP, Li J, Yadav SS and Tewari AK: Recent insights into NF-κB signalling pathways and the link between inflammation and prostate cancer. BJU Int. 114:168–176. 2014. View Article : Google Scholar
10	Luo JL, Kamata H and Karin M: IKK/NF-κB signaling: Balancing life and death-a new approach to cancer therapy. J Clin Invest. 115:2625–2632. 2005. View Article : Google Scholar :
11	Wu X, Gong S, Roy-Burman P, Lee P and Culig Z: Current mouse and cell models in prostate cancer research. Endocr Relat Cancer. 20:R155–R170. 2013. View Article : Google Scholar
12	Avancès C, Georget V, Térouanne B, Orio F, Cussenot O, Mottet N, Costa P and Sultan C: Human prostatic cell line PNT1A, a useful tool for studying androgen receptor transcriptional activity and its differential subnuclear localization in the presence of androgens and antiandrogens. Mol Cell Endocrinol. 184:13–24. 2001. View Article : Google Scholar
13	Dominska K, Piastowska-Ciesielska AW, Pluciennik E, Lachowicz-Ochedalska A and Ochedalski T: A comparison of the effects of angiotensin IV on androgen-dependent and androgen-independent prostate cancer cell lines. J Renin angiotensin Aldosterone Syst. 14:74–81. 2013. View Article : Google Scholar
14	Pfaffl MW, Horgan GW and Dempfle L: Relative expression soft-ware tool (REST) for group-wise comparison and statistical analysis of relative expression results in real-time PCR. Nucleic Acids Res. 30:e362002. View Article : Google Scholar :
15	Gasparian AV, Yao YJ, Kowalczyk D, Lyakh LA, Karseladze A, Slaga TJ and Budunova IV: The role of IKK in constitutive activation of NF-kappa B transcription factor in prostate carcinoma cells. J Cell Sci. 115:141–151. 2002.
16	Suh J, Payvandi F, Edelstein LC, Amenta PS, Zong WX, Gélinas C and Rabson AB: Mechanisms of constitutive NF-kappa B activation in human prostate cancer cells. Prostate. 52:183–200. 2002. View Article : Google Scholar
17	Alimirah F, Chen J, Basrawala Z, Xin H and Choubey D: DU-145 and PC-3 human prostate cancer cell lines express androgen receptor: Implications for the androgen receptor functions and regulation. FEBS Lett. 580:2294–2300. 2006. View Article : Google Scholar
18	Bidaux G, Roudbaraki M, Merle C, Crépin A, Delcourt P, Slomianny C, Thebault S, Bonnal JL, Benahmed M, Cabon F, et al: Evidence for specific TRPM8 expression in human prostate secretory epithelial cells: Functional androgen receptor requirement. Endocr Relat Cancer. 12:367–382. 2005. View Article : Google Scholar
19	Xu Y, Josson S, Fang F, Oberley TD, St Clair DK, Wan XS, Sun Y, Bakthavatchalu V, Muthuswamy A and St Clair WH: RelB enhances prostate cancer growth: Implications for the role of the nuclear factor-kappaB alternative pathway in tumorigenicity. Cancer Res. 69:3267–3271. 2009. View Article : Google Scholar :
20	Setlur SR, Royce TE, Sboner A, Mosquera JM, Demichelis F, Hofer MD, Mertz KD, Gerstein M and Rubin MA: Integrative microarray analysis of pathways dysregulated in metastatic prostate cancer. Cancer Res. 67:10296–10303. 2007. View Article : Google Scholar
21	Altuwaijri S, Lin HK, Chuang KH, Lin WJ, Yeh S, Hanchett LA, Rahman MM, Kang HY, Tsai MY, Zhang Y, et al: Interruption of nuclear factor kappaB signaling by the androgen receptor facilitates 12-O-tetradecanoylphorbolacetate-induced apoptosis in androgen-sensitive prostate cancer LNCaP cells. Cancer Res. 63:7106–7112. 2003.
22	Lessard L, Bégin LR, Gleave ME, Mes-Masson AM and Saad F: Nuclear localisation of nuclear factor-kappa B transcription factors in prostate cancer: An immunohistochemical study. Br J Cancer. 93:1019–1023. 2005. View Article : Google Scholar :
23	Josson S, Xu Y, Fang F, Dhar SK, St Clair DK and St Clair WH: RelB regulates manganese superoxide dismutase gene and resistance to ionizing radiation of prostate cancer cells. Oncogene. 25:1554–1559. 2006. View Article : Google Scholar :
24	Hatano K, Miyamoto Y, Nonomura N and Kaneda Y: Expression of gangliosides, GD1a, and sialyl paragloboside is regulated by NF-κB-dependent transcriptional control of α2,3-sialyltransferase III and VI in human castration-resistant prostate cancer cells. Int J Cancer. 129:1838–1847. 2011. View Article : Google Scholar
25	Wang J, Yi S, Zhou J, Zhang Y and Guo F: The NF-κB subunit RelB regulates the migration and invasion abilities and the radio-sensitivity of prostate cancer cells. Int J Oncol. 49:381–392. 2016.
26	Domingo-Domenech J, Mellado B, Ferrer B, Truan D, Codony-Servat J, Sauleda S, Alcover J, Campo E, Gascon P, Rovira A, et al: Activation of nuclearfactor-kappaB in human prostate carcinogenesis and association to biochemical relapse. Br J Cancer. 93:1285–1294. 2005. View Article : Google Scholar :
27	Seo SI, Song SY, Kang MR, Kim MS, Oh JE, Kim YR, Lee JY, Yoo NJ and Lee SH: Immunohistochemical analysis of NF-kappaB signaling proteins IKK epsilon, p50/p105, p52/p100 and RelA in prostate cancers. APMIS. 117:623–628. 2009. View Article : Google Scholar
28	Palvimo JJ, Reinikainen P, Ikonen T, Kallio PJ, Moilanen A and Jänne OA: Mutual transcriptional interference between RelA and androgen receptor. J Biol Chem. 271:24151–24156. 1996. View Article : Google Scholar
29	Nelius T, Filleur S, Yemelyanov A, Budunova I, Shroff E, Mirochnik Y, Aurora A, Veliceasa D, Xiao W, Wang Z and Volpert OV: Androgen receptor targets NFkappaB and TSP1 to suppress prostate tumor growth in vivo. Int J Cancer. 121:999–1008. 2007. View Article : Google Scholar :
30	Hunter JE, Leslie J and Perkins ND: c-Rel and its manyroles in cancer: An oldstory with new twists. Br J Cancer. 114:1–6. 2016. View Article : Google Scholar :
31	Weichert W, Boehm M, Gekeler V, Bahra M, Langrehr J, Neuhaus P, Denkert C, Imre G, Weller C, Hofmann HP, et al: Highexpression of RelA/p65 is associated with activation of nuclear factor-kappaB-dependent signaling in pancreatic cancer and marks a patient population with poor prognosis. Br J Cancer. 97:523–530. 2007. View Article : Google Scholar :
32	Sarkar DK, Jana D, Patil PS, Chaudhari KS, Chattopadhyay BK, Chikkala BR, Mandal S and Chowdhary P: Role of NF-κB as a prognostic marker in breast cancer: A pilot study in Indian patients. Indian J Surg Oncol. 4:242–247. 2013. View Article : Google Scholar :
33	Mukhopadhyay NK, Ferdinand AS, Mukhopadhyay L, Cinar B, Lutchman M, Richie JP, Freeman MR and Liu BC: Unraveling androgen receptor interactomes by an array-based method: discovery of proto-oncoprotein c-Rel as a negative regulator of androgen receptor. Exp Cell Res. 312:3782–3795. 2006. View Article : Google Scholar