Discovery of novel molecular characteristics and cellular biological properties in ameloblastoma

Autor: Sayuri Kondo, Akinobu Ota, Takayuki Ono, Sivasundaram Karnan, Md Wahiduzzaman, Toshinori Hyodo, Md Lutfur Rahman, Kunihiro Ito, Akifumi Furuhashi, Tomio Hayashi, Hiroyuki Konishi, Shinobu Tsuzuki, Yoshitaka Hosokawa, Yoshiaki Kazaoka
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Cancer Medicine, Vol 9, Iss 8, Pp 2904-2917 (2020)
Druh dokumentu: article
ISSN: 2045-7634
DOI: 10.1002/cam4.2931
Popis: Abstract Ameloblastoma is a rare odontogenic benign tumor accounting for less than 1% of head and neck tumors. Advanced next generation sequencing (NGS) analyses identified high frequency of BRAF V600E and SMO L412F mutations in ameloblastoma. Despite the existence of whole genomic sequence information from patients with ameloblastoma, entire molecular signature of and the characteristics of ameloblastoma cells are still obscure. In this study, we sought to uncover the molecular basis of ameloblastoma and to determine the cellular phenotype of ameloblastoma cells with BRAF mutations. Our comparative cDNA microarray analysis and gene set enrichment analysis (GSEA) showed that ameloblastoma exhibited a distinct gene expression pattern from the normal tissues: KRAS‐responsive gene set is significantly activated in ameloblastoma. Importantly, insulin like growth factor 2 (IGF2), a member of KRAS‐responsive genes, enhances the proliferation of an ameloblastoma cell line AMU‐AM1 with BRAF mutation. In addition, Toll‐like receptor 2 (TLR2) knockdown readily inactivated KRAS‐responsive gene sets as well as increases caspase activities, suggesting that TLR2 signaling may mediate cell survival signaling in ameloblastoma cells. Collectively, the findings may help to further clarify the pathophysiology of ameloblastoma and lead to the development of precision medicine for patients with ameloblastoma.
Databáze: Directory of Open Access Journals
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