Jump to main content
US EPA
United States Environmental Protection Agency
Search
Search
Main menu
Environmental Topics
Laws & Regulations
About EPA
Health & Environmental Research Online (HERO)
Contact Us
Print
Feedback
Export to File
Search:
This record has one attached file:
Add More Files
Attach File(s):
Display Name for File*:
Save
Citation
Tags
HERO ID
2509295
Reference Type
Journal Article
Title
The estrogen receptor signaling pathway activated by phthalates is linked with transforming growth factor-beta in the progression of LNCaP prostate cancer models
Author(s)
Lee, HR; Hwang, KA; Choi, KC
Year
2014
Is Peer Reviewed?
Yes
Journal
International Journal of Oncology
ISSN:
1019-6439
EISSN:
1791-2423
Book Title
Int J Oncol.
Volume
45
Issue
2
Page Numbers
595-602
Language
English
PMID
24858230
DOI
10.3892/ijo.2014.2460
Web of Science Id
WOS:000338484600015
Abstract
The distinct roles of estrogen receptors (ERs) related with androgen receptors (ARs) have been proposed in prostate cancer, while the involvement of transforming growth factor-beta (TGF-beta) has been reported in the progression of prostate cancer. In this study, we examined whether the TGF-beta signaling pathway is associated with ER signaling in LNCaP prostate cancer cells, which express ER alpha, ER beta and ARs. We determined whether the exposure to phthalates may induce prostate cancer progression by affecting molecular crosstalk between ER and TGF-beta signaling pathways. Cell viability was measured in LNCaP cells by MTT assay following treatment with di-n-buthyl phthalate (DBP). RT-PCR and immunoblot assay were performed to examine the expression levels of cell cycle-related genes and the TGF-beta signaling cascade. A mouse xenograft model of prostate cancer was generated, and immunohistochemical and BrdU assay were carried out to determine the effect of DBP in this mouse model. DBP, a type of phthalate, was shown to promote LNCaP cell proliferation by upregulating the gene expression of c-myc and cyclin D1 and by downregulating the expression of p21. DBP significantly reduced the protein expression of p-smad similarly to E2. These regulations caused by DBP were reversed by ICI 182,780, an ER antagonist, indicating that DBP may affect crosstalk between TGF-beta and ER signals. In an in vivo mouse model, tumor volume of mice exposed to DBP was increased. Number of cells in S phase of cell cycle was increased by DBP, while expression of p21 protein was reduced in the tissues of DBP-treated mice. These results indicate that DBP may induce the growth of LNCaP prostate cancer by acting on the crosstalk between TGF-beta and ER signaling pathways.
Keywords
phthalate; prostate cancer; estrogen receptor; transforming growth factor-beta; LNCaP cells
Tags
IRIS
•
Dibutyl Phthalate (DBP)
Database Searches
Pubmed
Web of Science
Litsearch September 2014 - February 2015
WOS
LitSearch Jan 2014 - Sep 2014
PubMed
Web of Science
Studies with Supporting Data
Mechanistic and genotoxicity studies
•
Phthalates – Targeted Search for Epidemiological Studies
Source – all searches
Pubmed
Excluded
Source – Mar 2015 Update (Private)
Pubmed
Source – Dec 2015 Update (Private)
Pubmed
PFAS
•
Additional PFAS (formerly XAgency)
Home
Learn about HERO
Using HERO
Search HERO
Projects in HERO
Risk Assessment
Transparency & Integrity