Oncogenic Activation of MAP Kinase by BRAF Pseudogene in Thyroid Tumors

• Published in: Neoplasia (New York, N.Y.) Vol. 11; no. 1; pp. 57 - 65
• Main Authors: Zou, Minjing, Baitei, Essa Y., Alzahrani, Ali S., Al-Mohanna, Futwan, Farid, Nadir R., Meyer, Brian, Shi, Yufei
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2009; Elsevier
• Subjects: Amino Acid Sequence; Animals; Base Sequence; Carcinoma - genetics; Carcinoma - metabolism; Carcinoma - pathology; CHO Cells; Cricetinae; Cricetulus; Enzyme Activation - physiology; Extracellular Signal-Regulated MAP Kinases - metabolism; Gene Expression Regulation, Neoplastic; Goiter - genetics; Goiter - metabolism; Humans; Mice; Mice, Nude; Molecular Sequence Data; NIH 3T3 Cells; Point Mutation - physiology; Proto-Oncogene Proteins B-raf - genetics; Proto-Oncogene Proteins B-raf - physiology; Pseudogenes - physiology; Thyroid Neoplasms - genetics; Thyroid Neoplasms - metabolism; Thyroid Neoplasms - pathology
• ISSN: 1476-5586; 1522-8002; 1476-5586; 1522-8002
• 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.