Activated fibroblast growth factor receptor 3 is an oncogene that contributes to tumor progression in multiple myeloma
Activated fibroblast growth factor receptor 3 is an oncogene that contributes to tumor progression in multiple myeloma
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DOI：
10.1182/blood.v97.3.729
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发表时间：
2001-02-01
期刊：
影响因子：
20.3
通讯作者：
Bergsagel, PL
中科院分区：
文献类型：
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作者：
Chesi, M;Brents, LA;Bergsagel, PL
t（4; 14）易位经常发生在多发性骨髓瘤（MM）中，并导致2种潜在癌基因FGFR 3的同时表达失调。（成纤维细胞生长因子受体3）和多发性骨髓瘤SET结构域蛋白/Wolf-Hirschhorn综合征候选基因1。14）易位表达功能性FGFR 3，其在某些情况下由引起致死性发育不良的相同突变组成性激活。与K-ras和N-ras的激活突变一样，其在约40%的MM患者中报道，然而，ras和FGFR 3的组成性激活不发生在相同的骨髓瘤细胞中。因此，这些蛋白质的激活形式似乎在肿瘤进展中共享重叠的作用，表明它们也共享信号级联，与这一预测一致，显示当以与在t（4; 14）骨髓瘤-是通过MAP激酶途径转化NIH 3 T3细胞的癌基因，NIH 3 T3细胞然后可以在裸鼠中产生肿瘤。因此，当FGFR 3在MM中过表达时，当在骨髓微环境中被FGF配体刺激时，不仅可能是致癌的，而且也是激活突变的靶点，所述突变使FGFR 3能够在肿瘤进展中发挥ras样作用。(C)2001年，美国血液学会。
The t(4;14) translocation occurs frequently in multiple myeloma (MM) and results in the simultaneous dysregulated expression of 2 potential oncogenes, FGFR3 (fibroblast growth factor receptor 3) from der(14) and multiple myeloma SET domain protein/Wolf-Hirschhorn syndrome candidate gene 1 from der(4), It is now shown that myeloma cells carrying a t(4;14) translocation express a functional FGFR3 that in some cases is constitutively activated by the same mutations that cause thanatophoric dysplasia, As with activating mutations of K-ras and N-ras, which are reported in approximately 40% of patients with MM, activating mutations of FGFR3 occur during tumor progression, However, the constitutive activation of ras and FGFR3 does not occur in the same myeloma cells, Thus the activated forms of these proteins appear to share an overlapping role in tumor progression, suggesting that they also share the signaling cascade, Consistent with this prediction, it is shown that activated FGFR3-when expressed at levels similar to those seen in t(4;14) myeloma-is an oncogene that acts through the MAP kinase pathway to transform NIH 3T3 cells, which can then generate tumors in nude mice, Thus, FGFR3,when overexpressed in MM, may be not only oncogenic when stimulated by FGF ligands in the bone marrow microenvironment, but is also a target for activating mutations that enable FGFR3 to play a ras-like role in tumor progression. (C) 2001 by The American Society of Hematology.