RESUMO
In mammalian cells, angiotensin II (AngII) binds to 2 distinct high-affinity plasma membrane receptors: angiotensin receptor 1 (AT1R) and angiotensin receptor 2 (AT2R). Healthy human endometrium from women of reproductive age expresses all of the components of the renin-angiotensin system. Many studies suggest that AngII, acting via AT1R, may have a role in the development and progression of cancer, which changes the expression of angiogenic factors, AngII and AT1R are correlated with the presence of endometrial cancer (EC). The aim of the current study was to identify the effects of AngII on the proliferation, cell cycle progression, apoptosis and mobility of ISHIKAWA, MFE296 and MFE280 EC cells with silenced AT1R. It also examines epithelial-mesenchymal transition markers by gene expression analysis. The obtained results suggest that the silencing of AT1R expression alters the migration and invasion ability of EC cells. However, this silencing is not sufficient to inhibit the effects of AngII on EC cells, suggesting that AngII plays a more complex role in the development of EC.
Assuntos
Angiotensina II/metabolismo , Neoplasias do Endométrio/metabolismo , Receptor Tipo 1 de Angiotensina/metabolismo , Apoptose/genética , Apoptose/fisiologia , Ciclo Celular/genética , Ciclo Celular/fisiologia , Linhagem Celular Tumoral , Neoplasias do Endométrio/genética , Feminino , Inativação Gênica/fisiologia , Humanos , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Receptor Tipo 1 de Angiotensina/genética , Cicatrização/genética , Cicatrização/fisiologiaRESUMO
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.
