Zou Minjing, Baitei Essa Y, Alzahrani Ali S, Al-Mohanna Futwan, Farid Nadir R, Meyer Brian, Shi Yufei
Department of Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia.
Neoplasia. 2009 Jan;11(1):57-65. doi: 10.1593/neo.81044.
Activating BRAF mutations have been reported in 40% of papillary thyroid carcinomas (PTCs). The involvement of BRAF pseudogene in thyroid tumorigenesis has not previously been studied. We investigated BRAF pseudogene expression in 68 thyroid tumors: 16 multinodular goiters, 43 classic PTCs, 6 follicular variants of PTC, and 3 anaplastic thyroid carcinomas. BRAF pseudogene function was studied by Western blots, soft agar assay, and tumorigenesis in nude mice. BRAF pseudogene expression was detected in 7 multinodular goiters, 18 classic PTC, and 1 follicular variants of PTC. There is an inverse correlation between BRAF pseudogene expression and BRAF mutation. The pseudogene transcripts were more frequently detected in tumors without BRAF mutation than those with BRAF mutation. Furthermore, BRAF pseudogene expression could activate the MAP kinase signaling pathway, transform NIH3T3 cells in vitro, and induce tumors in nude mice. These data suggest that BRAF pseudogene activation may play a role in thyroid tumor development.
在40%的甲状腺乳头状癌（PTC）中已报道存在激活型BRAF突变。此前尚未研究BRAF假基因在甲状腺肿瘤发生中的作用。我们调查了68例甲状腺肿瘤中BRAF假基因的表达情况，包括16例多结节性甲状腺肿、43例经典型PTC、6例PTC滤泡变体和3例间变性甲状腺癌。通过蛋白质免疫印迹法、软琼脂试验和裸鼠肿瘤发生实验研究了BRAF假基因的功能。在7例多结节性甲状腺肿、18例经典型PTC和1例PTC滤泡变体中检测到BRAF假基因表达。BRAF假基因表达与BRAF突变呈负相关。在无BRAF突变的肿瘤中比在有BRAF突变的肿瘤中更频繁地检测到假基因转录本。此外，BRAF假基因表达可激活丝裂原活化蛋白激酶信号通路，在体外转化NIH3T3细胞，并在裸鼠中诱导肿瘤。这些数据表明BRAF假基因激活可能在甲状腺肿瘤发展中起作用。
