[Cross-talk between Notch1 and epidermal growth factor receptor signalling in regulating cell proliferation of human tongue squamous carcinoma cells].
OBJECTIVE
To investigate the cross-talk between Notch1 and epidermal growth factor receptor (EGFR) signaling in regulating the cellular proliferation of human tongue squamous cell carcinoma (SCC).


METHODS
Human tongue SCC cell line Tca8113 cells was transiently transfected with the vector encoding exogenous intracellular fragment of Notch1 and the vector encoding the specific short hairpin RNA (shRNA) targeting EGFR respectively and were treated by AG1478, an inhibitor of receptor tyrosine kinases, for elucidating the effects of constitutive activation, EGFR gene silencing and blocking EGFR signaling upon cellular proliferation and expression of Notch1 and EGFR. The mRNA and protein levels of Notch1 and EGFR were detected by reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot, respectively. The cellular proliferation was evaluated by methyl thiazolyl tetrazolium (MTT) assay.


RESULTS
Constitutive activation of Notch1 resulted in inhibition of cellular proliferation, and up-regulation of Notch1 (1.102 +/- 0.135, 0.243 +/- 0.032, P < 0.05) but down-regulation of EGFR (0.083 +/- 0.009, 0.605 +/- 0.075, P < 0.05) at the the mRNA and protein levels. Silencing of EGFR gene resulted in inhibition of cell proliferation, and down-regulation of EGFR (0.148 +/- 0.019, 1.175 +/- 0.132, P < 0.05) but up-regulation of Notch1 (0.978 +/- 0.115, 0.083 +/- 0.009, P < 0.05) at the mRNA and protein levels. Blocking EGFR signaling had no significant effect upon EGFR expression (P > 0.05), but resulted in inhibition of cellular proliferation and up-regulation of Notch1 (P < 0.05) at the mRNA and protein levels.


CONCLUSIONS
There might be a cross-talk of bi-directional control between Notch1 and EGFR signaling in regulating the cellular proliferation of human tongue SCC cells.
Huang
Hong-jie
HJ
Department of Stomatology, Affiliated Hospital of Medical School, Hangzhou Normal University, Hangzhou 310015, China.
Ping
Fei-yun
FY
Hu
Ji-an
JA
Zhao
Shi-fang
SF
D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D051881:Receptor, Notch1 / Q000378:metabolism*; D015398:Signal Transduction; D014062:Tongue Neoplasms / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation
C497761:NOTCH1 protein, human; D051881:Receptor, Notch1; C512478:EGFR protein, human; D066246:ErbB Receptors