The impact of EGFR stimulation and inhibition on BPDE induced DNA fragmentation in oral/oropharyngeal mucosa in vitro.
Oral Oncol
; 47(12): 1141-7, 2011 Dec.
Article
in En
| MEDLINE
| ID: mdl-21903449
ABSTRACT
Still, the vast majority of head and neck squamous cell carcinoma (HNSCC) can be linked to the "traditional" risk factors tobacco smoke and alcohol consumption. These tumors are believed to be the results of multiple years of carcinogenic impact on upper aerodigestive tract mucosa. The frequent observation, that one patient suffers from several synchronous cancers, multiple local recurrences, and second primary tumors led to the concept of field cancerization, first introduced by Slaughter and colleagues in 1953. As underlying molecular events, genetic instability, loss of heterozygosity, amplification, deletion, up- and down-regulation of oncogenes and/or tumor suppressor genes were revealed. One of the best studied oncogenic features of head and neck carcinogenesis are high expression levels of epidermal growth factor receptor (EGFR). Enhanced expression of the receptor was detected in histologically normal mucosa from HNSCC patients and increasing levels during the progress from hyperplasia to dysplastic lesion and invasive carcinoma were demonstrated. Whereas nearly all of our knowledge about EGFR biology in HNSCC is based on preclinical and clinical studies investigating receptor inhibitors, little is known about cause and function of EGFR in premalignant mucosa. In this study we show, that EGFR stimulation significantly decreases carcinogen induced DNA damage in normal mucosa from HNSCC patients and that this effect is completely abrogated adding an anti-EGFR antibody before stimulation, while there was no effect in non-tumor controls. The effect of EGFR inhibition was contrary. In non-tumor controls, blocking the receptor with an antibody significantly decreased DNA damage, whereas in cases no effect was seen. Our results indicate an important role of the receptor during chemical carcinogenesis. On the basis of this study we suppose, that increasing EGFR levels during head and neck carcinogenesis can be interpreted as a physiological response to permanent carcinogen impact on the mucosa.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
DNA Damage
/
Mouth Neoplasms
/
Carcinoma, Squamous Cell
/
Oropharyngeal Neoplasms
/
ErbB Receptors
Type of study:
Observational_studies
/
Risk_factors_studies
Limits:
Adult
/
Aged
/
Aged80
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Oral Oncol
Journal subject:
NEOPLASIAS
Year:
2011
Document type:
Article
Affiliation country:
Germany