狗尿路上皮癌中 v-raf 小鼠肉瘤病毒癌基因同源物 B 突变 (V595E) 与 v-raf 小鼠肉瘤病毒癌基因同源物 B 磷酸化的并发症。

IF 1.1 4区 农林科学 Q2 Veterinary Canadian journal of veterinary research = Revue canadienne de recherche veterinaire Pub Date : 2022-10-01
Hirofumi Yamasaki, Yosuke Uematsu, Yuhei Hayashi, Masao Yamashita, Meina Tei, Kazuyuki Uchida, Kenichiro Ono, Hidehiro Hirao
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引用次数: 0

摘要

研究了磷酸化v-raf小鼠肉瘤病毒癌基因同源物B(pBRAF)和磷酸化细胞外信号调节激酶1/2(pERK1/2)在有或没有BRAF基因突变(V595E)的狗尿路上皮癌(UC)中的表达情况。在 10 例 V595E(-)的 UC 中,有 8 例报告了肿瘤细胞的 pBRAF 细胞质免疫反应,其中 7 例为中度反应,1 例为高度反应。在 5 个病例中检测到了针对 pBRAF 的核免疫反应;然而,这些反应是非特异性的,因为 pBRAF 仅限于细胞质中。此外,在 7 个病例中检测到针对肿瘤细胞 pERK1/2 的细胞质免疫反应阳性,在 6 个病例中检测到针对 ERK1/2 的核免疫反应阳性。在 13 例 V595E(+)型 UC 病例中,所有 13 例均检测到针对肿瘤细胞 pBRAF 的细胞质免疫反应,10 例检测到针对 pBRAF 的核免疫反应;然而,核免疫反应是非特异性的。在所有 13 个病例中都检测到了针对肿瘤细胞 pERK1/2 的细胞质免疫反应,在所有病例中也检测到了针对 pERK1/2 的核免疫反应。由于核 pERK1/2 表明有丝分裂原激活蛋白激酶通路中的信号转导过程是渐进的,因此 V595E (+) UC 可能正处于生长阶段。本研究中检测到的 pBRAF 在 Thr598/Ser601 处的可能磷酸化位点是上游大鼠肉瘤病毒癌基因同源物(RAS)信号通路的主要和重要位点。在人类癌症中,BRAF 突变从未与致癌的 RAS 相吻合。据我们所知,这是第一份在患有 UC 的狗中同时出现 BRAF 突变(V595E)和 pBRAF 表达(位于 Thr598/Ser601)的报告。
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Coincidence of v-raf murine sarcoma viral oncogene homolog B mutation (V595E) with phosphorylated v-raf murine sarcoma viral oncogene homolog B in urothelial carcinoma in dogs.

Expression of phosphorylated v-raf murine sarcoma viral oncogene homolog B (pBRAF) and phosphorylated extracellular signal-regulated kinase1/2 (pERK1/2) were investigated in urothelial carcinoma (UC) in dogs with or without the BRAF gene mutation (V595E). Among the 10 cases of UC with V595E (-), cytoplasmic immunoreactivity against pBRAF of neoplastic cells was reported in 8, with 7 displaying moderate reactivity and 1 displaying intense reactivity. Nuclear immunoreactivity against pBRAF was detected in 5 cases; however, these reactivities were non-specific, due to pBRAF being limited in the cytoplasm. In addition, positive cytoplasmic immunoreactivity against pERK1/2 of neoplastic cells was detected in 7 cases and nuclear immunoreactivity against ERK1/2 was detected in 6 cases. Among the 13 cases of UC with V595E (+), cytoplasmic immunoreactivity against pBRAF of neoplastic cells was detected in all 13 cases and nuclear immunoreactivity against pBRAF was detected in 10 cases; however, the nuclear immunoreactivity was non-specific. Cytoplasmic immunoreactivity against pERK1/2 of neoplastic cells was detected in all 13 cases and nuclear immunoreactivity against pERK1/2 was also detected in all cases. As nuclear pERK1/2 indicates a progressive signaling process in the mitogen-activated protein kinase pathway, V595E (+) UC might be in its growing stage. Probable phosphorylated sites of pBRAF at Thr598/Ser601, detected in this study, are major and essential sites of the upstream rat sarcoma viral oncogene homolog (RAS) signaling pathway. In human cancers, the BRAF mutation never coincides with oncogenic RAS. To our knowledge, this is the first report on the simultaneous occurrence of the BRAF mutation (V595E) and pBRAF expression (at Thr598/Ser601) in dogs with UC with V595E (+).

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来源期刊
CiteScore
1.80
自引率
0.00%
发文量
58
审稿时长
>24 weeks
期刊介绍: The Canadian Journal of Veterinary Research, published by the Canadian Veterinary Medical Association, is Canada''s only veterinary research publication. This quarterly peer-reviewed online-only journal has earned a wide international readership through the publishing of high quality scientific papers in the field of veterinary medicine. The Journal publishes the results of original research in veterinary and comparative medicine.
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