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  • Title: Identification of a novel partner gene, KIAA1217, fused to RET: Functional characterization and inhibitor sensitivity of two isoforms in lung adenocarcinoma.
    Author: Lee MS, Kim RN, I H, Oh DY, Song JY, Noh KW, Kim YJ, Yang JW, Lira ME, Lee CH, Lee MK, Kim YD, Mao M, Han J, Kim J, Choi YL.
    Journal: Oncotarget; 2016 Jun 14; 7(24):36101-36114. PubMed ID: 27150058.
    Abstract:
    REarranged during Transfection (RET) fusion genes are detected in approximately 1% of lung adenocarcinomas and known primarily as oncogenic driver factors. Here, we found a novel RET fusion gene, KIAA1217-RET, and examined the functional differences of RET51 and RET9 protein, fused with KIAA1217 in cancer progression and drug response. KIAA1217-RET, resulting from the rearrangement of chromosome 10, was generated by the fusion of KIAA1217 exon 11 and RET exon 11 from a non-small cell lung cancer patient. Expression of this gene led to increased cell growth and invasive properties through activations of the PI3K/AKT and ERK signaling pathways and subsequently enabled oncogenic transformation of lung cells. We observed that cells expressing KIAA1217-RET9 fusion protein were more sensitive to vandetanib than those expressing KIAA1217-RET51 and both isoforms attenuated cellular growth via cell cycle arrest. These results demonstrated that KIAA1217-RET fusion represents a novel oncogenic driver gene, the products of which are sensitive to vandetanib treatment, and suggested that the KIAA1217-RET-fusion gene is a promising target for lung cancer treatment.
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