pgp - publications

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1. Anticancer Res. 2012 May;32(5):1639-48.

EGFR and P-GP Expression in Oropharyngeal Mucosa in Relation to Smoking.

Baumeister P, Märte M, Reiter M, Welz C, Schwenk-Zieger S, Harréus U.

University of Munich Hospital, Marchioninistr. 15, 81377 Munich, Germany.
Philipp.Baumeister@med.uni-muenchen.de.

BACKGROUND: About two thirds of head and neck squamous cell carcinoma (HNSCC)
cases are attributable to heavy tobacco and alcohol consumption. Tobacco
carcinogens cause cellular damage in large areas of the upper aerodigestive tract
mucosa and contribute to distinct molecular changes, such as increasing levels of
epidermal growth factor receptor (EGFR), during carcinogenesis. P-Glycoprotein
(P-GP) is a multidrug-resistance transporter protein capable of extruding not
only cytotoxic drugs, but also certain tobacco-related carcinogens. EGFR plays a
major role in the transcriptional and functional regulation of P-GP and previous
studies in our laboratory showed that stimulation of EGFR protection protected
oropharyngeal cells from a carcinogen that is substrate of P-GP. Therefore, we
evaluated expression levels of EGFR and P-GP and looked for a possible
association with the smoking status of patients.
MATERIALS AND METHODS: Tissue cultures of healthy oropharyngeal mucosa were
produced from 30 patients undergoing surgery at our Department. Expression levels
of EGFR on P-GP were determined by immunohistochemical staining. To evaluate
possible influences of EGFR on P-GP expression, we stimulated the receptor using
transforming growth factor alpha (TGF-α) for 24, 48 and 72 h.
RESULTS: Current and former smokers had significantly higher EGFR/P-GP levels
than never smokers. While EGFR expression was detected in almost all samples,
P-GP expression was largely restricted to former and current smokers. TGF-α had
no detectable effect on EGFR/P-GP levels.
CONCLUSION: These results show an association between tobacco use and levels of
both proteins. Since both these proteins are involved in drug resistance of head
and neck cancer, this study might help to further understand the differences in
response to therapy and prognosis of tobacco-related and -unrelated cancer.

PMID: 22593442 [PubMed - in process]