A common effect of angiotensin II and relaxin 2 on the PNT1A normal prostate epithelial cell line

J Physiol Biochem. 2016 Sep;72(3):381-92. doi: 10.1007/s13105-016-0489-1. Epub 2016 Apr 27.

Abstract

The prostate gland is a part of the male reproductive tract which produces both angiotensin II (Ang II) and relaxin 2 (RLN2). The present study analyzes the effect of both these peptide hormones at concentration 10(-8)M on viability, proliferation, adhesion, migration, and invasion of normal prostate epithelial cells (PNT1A). Improved survival in two- and three-dimensional cell cultures was noted as well as visual changes in colony size and structure in Geltrex™. Stimulatory influence on cell viability of each peptide applied single was lower than in combination. Enhanced survival of PNT1A cells appears to be associated with increased BCL2/BAX messenger RNA (mRNA) expression ratio. Modulation of cell spreading and cell-extracellular matrix adhesion dynamics were also altered as an influence of tested hormone application. However, long-term Ang II and RLN2 effects may lead to an increase of normal prostate cell migration and invasion abilities. Moreover, gelatin zymography revealed that both gelatinases A and B were augmented by Ang II treatment, whereas RLN2 significantly stimulated only MMP-9 secretion. These results support the hypothesis that deregulation of locally secreted peptide hormones such as Ang II and RLN2 may take part in the development of certain cancers, including prostate cancer. Moreover, the observed ability of relaxin 2 to act as a regulator of mRNA expression levels not only LGR7 but also classic angiotensin receptors suggested that renin-angiotensin system and relaxin family peptide system are functionally linked.

Keywords: Angiotensin II; PNT1A; Peptide hormones, prostate gland; Relaxin 2.

Publication types

  • Comparative Study

MeSH terms

  • Angiotensin II / metabolism*
  • Apoptosis*
  • Basement Membrane / physiology*
  • Cell Adhesion
  • Cell Line, Transformed
  • Cell Movement
  • Cell Proliferation
  • Cell Survival
  • Gene Expression Regulation*
  • Humans
  • Male
  • Matrix Metalloproteinase 2 / chemistry
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / chemistry
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Mucous Membrane / cytology
  • Mucous Membrane / metabolism*
  • Prostate / cytology
  • Prostate / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / agonists
  • Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • RNA, Messenger / metabolism
  • Receptor, Angiotensin, Type 1 / agonists
  • Receptor, Angiotensin, Type 1 / genetics
  • Receptor, Angiotensin, Type 1 / metabolism
  • Receptor, Angiotensin, Type 2 / agonists
  • Receptor, Angiotensin, Type 2 / genetics
  • Receptor, Angiotensin, Type 2 / metabolism
  • Receptors, G-Protein-Coupled / agonists
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism
  • Receptors, Peptide / agonists
  • Receptors, Peptide / genetics
  • Receptors, Peptide / metabolism
  • Relaxin / metabolism*
  • bcl-2-Associated X Protein / agonists
  • bcl-2-Associated X Protein / antagonists & inhibitors
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism

Substances

  • AGTR1 protein, human
  • BAX protein, human
  • BCL2 protein, human
  • Proto-Oncogene Proteins c-bcl-2
  • RLN2 protein, human
  • RNA, Messenger
  • RXFP1 protein, human
  • Receptor, Angiotensin, Type 1
  • Receptor, Angiotensin, Type 2
  • Receptors, G-Protein-Coupled
  • Receptors, Peptide
  • bcl-2-Associated X Protein
  • Angiotensin II
  • Relaxin
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • MMP9 protein, human
  • Matrix Metalloproteinase 9