Department of Biochemistry, New York University Langone Medical Center, New York, NY, USA.
Surgery. 2010 Dec;148(6):1282-7; discussion 1287. doi: 10.1016/j.surg.2010.09.028.
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.
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.
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.
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.
BRAF 突变激活丝裂原活化蛋白激酶（MAPK）通路，通常赋予甲状腺癌（TC）侵袭性表型。Spry2 是 MAPK 通路的诱导性负反馈调节因子。本研究旨在探讨 Spry2 在 TC 中的作用。
分析 TC 细胞系中 Spry2 表达和 MAPK 通路激活情况。用 MEK 抑制剂和 Spry2 短发夹 RNA 处理细胞。分析 Spry2 表达和 MEK/ERK 磷酸化（pMEK、pERK）情况。分析 30 例人甲状腺乳头状癌组织中 MAPK 通路激活突变和 Spry2 表达情况。
BRAF V600E 突变（BRAF+）细胞中存在较高的基础 pMEK 水平和 Spry2 表达。BRAF+细胞中 MEK 抑制导致 Spry2 表达降低，pMEK/pERK 水平降低。在我们的组织样本中，有 10 例甲状腺乳头状癌存在 BRAF 突变，仅在 BRAF+肿瘤中发现 Spry2 表达增加。
Spry2 表达与体外和人类组织中的 BRAF 状态相关。Spry2 可能作为 BRAF+TC 中 MAPK 通路的负反馈调节因子。Spry2 表达增加可能作为 MAPK 通路激活的替代标志物，具有预后和治疗意义。
