Downregulation of Notch1 and its potential correlation with epidermal growth factor receptor signalling in tongue squamous cell carcinoma.
We investigated the expression of Notch1 in human oral squamous cell carcinoma (SCC) and explored its potential correlation with epidermal growth factor receptor (EGFR) signalling in oral SCC. Paraffin sections of primary SCC of the tongue and normal mucosa were screened immunohistochemically for Notch1 and EGFR proteins. Human SCC of the tongue Tca8113 cells were treated with AG1478 to block EGFR signalling, and were transfected with the vector that encodes the specific short hairpin RNA (shRNA) that targets EGFR. In SCC of the tongue expression of Notch1 was cancelled except in sites of squamous metaplasia where it was raised, while expression of EGFR was found in the peripheral cells of carcinomas, but not in sites of squamous metaplasia. In normal tongue mucosa, Notch1 was expressed mainly in the stratum corneum, but not in the stratum basale, while EGFR was expressed mainly in the stratum basale, but not in the stratum granulosum or stratum corneum. The blocking of EGFR signalling or the silencing of the EGFR gene resulted in upregulation of Notch1 at mRNA and protein levels in Tca8113 cells. These observations suggest that downregulation of Notch1 in oral SCC may be associated with upregulation of EGFR signalling.
Huang
Hong-jie
HJ
Department of Oral and Maxillofacial Surgery, School of Stomatology, Zhejiang University, Hangzhou, PR China.
Ping
Fei-yun
FY
Hu
Ji-an
JA
Zhao
Shi-fang
SF
D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000473:pathology; D066246:ErbB Receptors / Q000032:analysis* / Q000037:antagonists & inhibitors; D020868:Gene Silencing; D006801:Humans; D055029:Inverted Repeat Sequences / Q000235:genetics; D008679:Metaplasia; D009061:Mouth Mucosa / Q000473:pathology; D010957:Plasmids / Q000235:genetics; D011799:Quinazolines; D012313:RNA / Q000235:genetics; D051881:Receptor, Notch1 / Q000032:analysis*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014059:Tongue / Q000473:pathology; D014062:Tongue Neoplasms / Q000473:pathology*; D014162:Transfection; D020032:Tyrphostins / Q000494:pharmacology; D015854:Up-Regulation
D004791:Enzyme Inhibitors; C497761:NOTCH1 protein, human; D011799:Quinazolines; D051881:Receptor, Notch1; D020032:Tyrphostins; C101044:RTKI cpd; D012313:RNA; D066246:ErbB Receptors