Association and regulation of protein factors of field effect in prostate tissues.
Int J Oncol
; 49(4): 1541-1552, 2016 Oct.
Article
em En
| MEDLINE
| ID: mdl-27634112
ABSTRACT
Field effect or field cancerization denotes the presence of molecular aberrations in structurally intact cells residing in histologically normal tissues adjacent to solid tumors. Currently, the etiology of prostate fieldeffect formation is unknown and there is a prominent lack of knowledge of the underlying cellular and molecular pathways. We have previously identified an upregulated expression of several protein factors representative of prostate field effect, i.e., early growth response-1 (EGR1), platelet-derived growth factorA (PDGFA), macrophage inhibitory cytokine1 (MIC1), and fatty acid synthase (FASN) in tissues at a distance of 1 cm from the visible margin of intracapsule prostate adenocarcinomas. We have hypothesized that the transcription factor EGR1 could be a key regulator of prostate fieldeffect formation by controlling the expression of PDGFA, MIC1, and FASN. Taking advantage of our extensive quantitative immunofluorescence data specific for EGR1, PDGFA, MIC1, and FASN generated in diseasefree, tumoradjacent, and cancerous human prostate tissues, we chose comprehensive correlation as our major approach to test this hypothesis. Despite the static nature and sample heterogeneity of association studies, we show here that sophisticated data generation, such as by spectral image acquisition, linear unmixing, and digital quantitative imaging, can provide meaningful indications of molecular regulations in a physiologically relevant in situ environment. Our data suggest that EGR1 acts as a key regulator of prostate field effect through induction of proproliferative (PDGFA and FASN), and suppression of proapoptotic (MIC1) factors. These findings were corroborated by computational promoter analyses and cell transfection experiments in noncancerous prostate epithelial cells with ectopically induced and suppressed EGR1 expression. Among several clinical applications, a detailed knowledge of pathways of field effect may lead to the development of targeted intervention strategies preventing progression from pre-malignancy to cancer.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Idioma:
En
Revista:
Int J Oncol
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Estados Unidos