Spry2 expression correlates with BRAF mutation in thyroid cancer.
BACKGROUND
BRAF mutations activate the mitogen-activated protein kinase pathway and often confer an aggressive thyroid cancer (TC) phenotype. Spry2 is an inducible negative feedback regulator of the mitogen-activated protein kinase (MAPK) pathway. The aim of this study was to investigate the role of Spry2 in TC.


METHODS
TC cell lines were analyzed for Spry2 expression and MAPK pathway activation. Cells were treated with MEK inhibitor and Spry2 small hairpin RNA. Cells were analyzed for Spry2 expression and MEK/ERK phosphorylation (pMEK, pERK). Thirty human papillary TCs were analyzed for mitogen-activated protein kinase pathway activating mutations and Spry2 expression.


RESULTS
Increased baseline pMEK levels and Spry2 expression was found in BRAF V600E mutant (BRAF+) cells. MEK inhibition in BRAF+ cells showed decreased Spry2 expression and decreased pMEK/pERK levels. From our tissue samples, 10 papillary TCs had BRAF mutation, and increased Spry2 expression was found only in BRAF+ tumors.


CONCLUSIONS
Spry2 expression correlates with BRAF status in vitro and in human tissue. Spry2 may serve as a negative feedback regulator of the mitogen-activated protein kinase pathway in BRAF+ TC. Increased Spry2 expression may serve as a surrogate marker of mitogen-activated protein kinase pathway activation with prognostic and therapeutic implications.
Department of Biochemistry, New York University Langone Medical Center, New York, NY, USA.
Lizhong
L
Xu
Jun Liang
JL
Zhou
Michael
M
Cohen
Dafna
D
Bar-Sagi
Kepal N
KN
Patel
D001483:Base Sequence; D045744:Cell Line, Tumor / Q000473:pathology; D003470:Culture Media; D005786:Gene Expression Regulation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008565:Membrane Proteins; D009154:Mutation; D016133:Polymerase Chain Reaction / Q000379:methods; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D034622:RNA Interference; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D034741:RNA, Small Interfering / Q000235:genetics; D013964:Thyroid Neoplasms / Q000235:genetics*
D003470:Culture Media; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D012334:RNA, Neoplasm; D034741:RNA, Small Interfering; C485561:SPRY2 protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf