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 reninangiotensin 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 factorκB subunit 1 (NFKB1), nuclear factorκB subunit 2 (NFKB2), REL protooncogene nuclear factorκB p65 subunit (REL), RELA protooncogene nuclear factorκB subunit (RELA) and RELB protooncogene nuclear factorκB subunit (RELB) mRNA caused by Ang II and RLN2. The members of NFkB family are involved in many processes associated with cancer development and metastasis. Reverse transcriptionquantitative polymerase chain reaction analysis identified that both peptide hormones have an influence on the relative expression of nuclear factorκB. Following treatment with either peptide, NFKB1 expression was downregulated in all prostate cancer cell lines (LNCaP, DU145 and PC3), but not in normal epithelial cells (PNT1A). Conversely, RELB mRNA was enhanced only in noncancerous 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 androgendependent cell line while RLN2 enhanced NFKB2 and RELA mRNA in androgenindependent cells (DU145). Further research is needed to understand the regulation of NFκB family members by key reninangiotensin system and RFPS peptides in prostate cancer cells; however, prostate carcinogenesis appears to be influenced by the balance between the crossregulation of nuclear factorκB (NFκB) and androgen receptor pathways by Ang II and relaxin 2.
Subject(s)
Angiotensin II/pharmacology , Gene Expression/drug effects , NF-kappa B/metabolism , Prostate/drug effects , Prostatic Neoplasms/drug therapy , RNA, Messenger/metabolism , Relaxin/pharmacology , Cell Line , Cell Line, Tumor , Humans , Male , Prostate/metabolism , Prostatic Neoplasms/metabolism , Proto-Oncogenes/drug effects , Renin-Angiotensin System/drug effects , Transcription Factor RelA/metabolismABSTRACT
Endometrial cancer (EC) is the most common gynecological malignancy. Alterations of angiogenic factors including angiotensin (AngII) or VEGF are observed in EC. Expression of angiotensin receptor 1 (AT1) is correlated with EC. Moreover, the expression of VEGF is up-regulated by AngII. Androgens are involved in the pathogenesis of EC. Genetic variations in androgen receptor (AR) gene may increase EC risk. This review proved strong correlation among EC, AngII, its receptors and AR, where AT influence on AR and, as a result, induce the expression of genes related to carcinogenesis.