BRAF V600E ONCOGENE EXPRESSION AND TLR4 ACTIVATION MODULATE EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) IN THYROID TRANSFORMED CELLS

PEYRET V; NAZAR M; PELLIZAS CG; MASINI-REPISO AM

Florianópolis

Congreso; XV Congress of the Latin American Thyroid Society (LATS); 2013

Latin American Thyroid Society (LATS)

Background. Increased expression of Epidermal Growth Factor Receptor (EGFR) in human thyroid carcinoma is considered a marker of tumor progression. The Toll-like receptor 4 (TLR4) has been involved in several human carcinomas. We have demonstrated an increased TLR4 expression in human thyroid carcinoma tissues and cell lines. We demonstrated that the induction of the oncogene BRAF V600E in the normal rat thyroid cell line PCCL3 enhances TLR4 expression. A transactivation of the EGFR pathway after activation of TLR4 has been described in various human cancers. Methods. Culture of human thyroid anaplastic carcinoma cell line 8505c; PC-BRAF cell line, a TET-ON system in which PCCL3 thyroid cells express BRAF V600E oncogene when treated with doxycycline; Western Blot (WB). Objective. Analyze the effect of BRAF V600E oncogene induction on EGFR expression in PCCL3 and a possible interaction among TLR4 stimulation and EGFR activation. Results. High EGFR expression was displayed (WB) in the BRAF V600E-expressing 8505 cells. When these cells where stimulated by the TLR4 ligand lipopolysaccharide (LPS) an increase of EGFR phosphorylation was observed at 30 and 45 min. The expression of EGFR in time course experiments where doxycycline was added to the culture medium of PC-BRAF cells for three days showed that the presence of the BRAF V600E oncogene increased EGFR expression in PC-BRAF cells. Conclusions. It was concluded that the high EGFR expression in human tumor cells could be associated with BRAF V600E oncogene expression. A TLR4-dependent EGFR transactivation in human thyroid cancer cells is suggested.