The role of ZEB1 in the inflammation-induced promotion of EMT in HNSCC.
OBJECTIVE
To determine the role of ZEB1 in the inflammation-induced promotion of the epithelial-mesenchymal transition (EMT) in head and neck squamous cell carcinoma (HNSCC).


METHODS
A molecular biology study. Real-time quantitative reverse-transcriptase polymerase chain reaction (RT-PCR), Western blot analysis, and immunohistochemical staining of human HNSCC tissue sections were used to determine how inflammation affects the transcriptional repressor, ZEB1.


METHODS
An academic hospital laboratory.


METHODS
Relative ZEB1 RNA levels were determined by RT-PCR, and protein expression was evaluated in situ by immunohistochemical staining of human HNSCC tissue sections.


RESULTS
IL-1beta-treated HNSCC cell lines demonstrated a significant decrease in E-cadherin mRNA and an increase in the mRNA expression of the transcriptional repressor ZEB1. IL-1beta exposure led to enhanced ZEB1 binding at the chromatin level, as determined by chromatin immunoprecipitation assays (ChIP). An inverse relationship between ZEB1 and E-cadherin was demonstrated in situ by immunohistochemical staining of human HNSCC tissue sections.


CONCLUSIONS
Our recent investigations indicate that inflammatory mediators are potent regulators of EMT in HNSCC. This is the first report indicating the role of ZEB1 in the inflammation-induced promotion of EMT in HNSCC. This newly defined pathway for transcriptional regulation of E-cadherin in HNSCC has important implications for targeted chemoprevention and therapy.
Dohadwala
Mariam
M
Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Wang
Guanyu
G
Heinrich
Eileen
E
Luo
Jie
J
Lau
Ontario
O
Shih
Hubert
H
Munaim
Qahera
Q
Lee
Gina
G
Hong
Longsheng
L
Lai
Chi
C
Abemayor
Elliot
E
Fishbein
Michael C
MC
Elashoff
David A
DA
Dubinett
Steven M
SM
St John
Maie A
MA
D015820:Cadherins / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000032:analysis; D004847:Epithelial Cells / Q000473:pathology*; D006258:Head and Neck Neoplasms / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D007249:Inflammation / Q000473:pathology*; D053583:Interleukin-1beta / Q000494:pharmacology; D008648:Mesoderm / Q000473:pathology*; D012313:RNA / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D015820:Cadherins; D053583:Interleukin-1beta; D014157:Transcription Factors; D012313:RNA; D051546:Cyclooxygenase 2