Increased expression of nuclear factor E2 p45-related factor 2 (NRF2) in head and neck squamous cell carcinomas.
BACKGROUND
Head and neck squamous cell carcinoma (HNSCC) continues to cause significant morbidity and mortality. Overexpression of specific phase II gene products may represent an important biomarker. One regulator of phase II gene expression is the transcription factor nuclear factor E2 p45-related factor 2 (Nrf2). Nrf2 expression was evaluated in HNSCC, to determine whether it might serve as a biomarker for early detection of disease.


METHODS
A tissue microarray was constructed of 141 HNSCC biopsy cores from 47 HNSCCs. In addition, histologically normal squamous mucosa was obtained from 7 patients. Protein expression was evaluated by immunohistochemistry.


RESULTS
Nrf2 expression was increased in 91.5% of tumors. Expression of thioredoxin, a Nrf2-reguated gene product, was elevated in 75% of tumors. Keap1, which regulates the rate of Nrf2 ubiquitination and degradation, was relatively overexpressed in HNSCC compared with normal mucosa.


CONCLUSIONS
Nrf2 expression may be a possible HNSCC candidate biomarker.
Stacy
Donnie R
DR
Department of Radiation Oncology, Vanderbilt University School of Medicine, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee 37232, USA.
Ely
Kim
K
Massion
Pierre P
PP
Yarbrough
Wendell G
WG
Hallahan
Dennis E
DE
Sekhar
Konjeti R
KR
Freeman
Michael L
ML
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D000072019:Kelch-Like ECH-Associated Protein 1; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*
D014408:Biomarkers, Tumor; D047908:Intracellular Signaling Peptides and Proteins; C431364:KEAP1 protein, human; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2