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乳腺癌中异柠檬酸脱氢酶的相对同工型表达水平：IDH2是MDA-MB-231细胞中的一个潜在靶点。

The relative isoform expression levels of isocitrate dehydrogenase in breast cancer: IDH2 is a potential target in MDA-MB-231 cells.

作者信息

Piao Shuyu, Kim Seonhee, Seo Youngduk, Lee Jinsun, Jeon Sunhee, Vu Giang-Huong, Yeo Min-Kyung, Kim Cuk-Seong

机构信息

Department of Physiology and Medical Science, Chungnam National University College of Medicine, Daejeon, Korea.

Department of Nuclear Medicine, Chungnam National University Sejong Hospital, Sejong, Korea.

出版信息

Korean J Clin Oncol. 2023 Dec;19(2):60-68. doi: 10.14216/kjco.23011. Epub 2023 Dec 31.

DOI:10.14216/kjco.23011
PMID:38229490
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10792364/
Abstract

PURPOSE

The isocitrate dehydrogenase (IDH) family plays an essential role in metabolism and energy production. The relative expression levels of IDH isoforms (IDH1, IDH2, and IDH3) have prognostic significance in several malignancies, including breast carcinoma. However, the IDH isozyme expression levels in different cancer stages and types have not been determined in breast carcinoma tissues.

METHODS

We analyzed the messenger RNA (mRNA) and protein levels of IDH (IDH1, IDH2, and IDH3A) and α-ketoglutarate (α-KG) in 59 breast carcinoma tissues.

RESULTS

The mRNA level of IDH2 was significantly increased at stages 2 and 3 in triple-negative and (ER-/PR-/HER+) breast cancers. However, the elevated α-KG level was only observed in stages 2 and 3, with no differences in the various breast carcinoma types. Western blotting analysis showed that IDH2 protein expression increased in the patient tissues and cell lines. An in vitro study showed IDH2 downregulation in the triple-negative breast cancer cell line MDA-MB-231 that inhibited cell proliferation and migration and induced cell cycle arrest in the G0/G1 phase.

CONCLUSION

These findings suggest that different from IDH1 and IDH3, IDH2 is more highly expressed in stages 2 and 3 breast cancer tissues, especially in triple-negative breast cancer. IDH2 potentially serves as a target to detect unknown mechanisms in breast cancer.

摘要

目的

异柠檬酸脱氢酶（IDH）家族在代谢和能量产生中起关键作用。IDH亚型（IDH1、IDH2和IDH3）的相对表达水平在包括乳腺癌在内的多种恶性肿瘤中具有预后意义。然而，乳腺癌组织中不同癌症阶段和类型的IDH同工酶表达水平尚未确定。

方法

我们分析了59例乳腺癌组织中IDH（IDH1、IDH2和IDH3A）和α-酮戊二酸（α-KG）的信使核糖核酸（mRNA）和蛋白质水平。

结果

在三阴性和（雌激素受体阴性/孕激素受体阴性/人表皮生长因子受体2阳性）乳腺癌的2期和3期，IDH2的mRNA水平显著升高。然而，α-KG水平升高仅在2期和3期观察到，在各种乳腺癌类型中无差异。蛋白质印迹分析显示，患者组织和细胞系中IDH2蛋白表达增加。一项体外研究显示，三阴性乳腺癌细胞系MDA-MB-231中IDH2下调，抑制细胞增殖和迁移，并诱导细胞周期停滞在G0/G1期。

结论

这些发现表明，与IDH1和IDH3不同，IDH2在2期和3期乳腺癌组织中表达更高，尤其是在三阴性乳腺癌中。IDH2可能作为检测乳腺癌未知机制的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10d5/10792364/5a1c1ea11e61/kjco-19-2-60f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10d5/10792364/66b4ee7dac2d/kjco-19-2-60f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10d5/10792364/cf83402a313e/kjco-19-2-60f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10d5/10792364/f554b7ba1666/kjco-19-2-60f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10d5/10792364/6c7eb8892456/kjco-19-2-60f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10d5/10792364/5a1c1ea11e61/kjco-19-2-60f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10d5/10792364/66b4ee7dac2d/kjco-19-2-60f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10d5/10792364/cf83402a313e/kjco-19-2-60f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10d5/10792364/f554b7ba1666/kjco-19-2-60f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10d5/10792364/6c7eb8892456/kjco-19-2-60f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10d5/10792364/5a1c1ea11e61/kjco-19-2-60f5.jpg

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Functional and topographic effects on DNA methylation in IDH1/2 mutant cancers.
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