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在乳腺癌中,胆碱和 β-连环蛋白通路增强之间是否存在关联?一项基于磁共振波谱和 ELISA 的初步研究。

Is there an association between enhanced choline and β-catenin pathway in breast cancer? A pilot study by MR Spectroscopy and ELISA.

机构信息

Department of NMR & MRI Facility, All India Institute of Medical Sciences, New Delhi, 110029, India.

Department of Biophysics, All India Institute of Medical Sciences, New Delhi, 110029, India.

出版信息

Sci Rep. 2017 May 22;7(1):2221. doi: 10.1038/s41598-017-01459-z.

Abstract

Total choline (tCho) was documented as a biomarker for breast cancer diagnosis by in vivo MRS. To understand the molecular mechanisms behind elevated tCho in breast cancer, an association of tCho with β-catenin and cyclin D1 was evaluated. Hundred fractions from 20 malignant, 10 benign and 20 non-involved breast tissues were isolated. Cytosolic and nuclear expressions of β-catenin and cyclin D1 were estimated using ELISA. Higher tCho was seen in malignant compared to benign tissues. Malignant tissues showed higher cytosolic and nuclear β-catenin expressions than benign and non-involved tissues. Within malignant tissues, β-catenin and cyclin D1 expressions were higher in the nucleus than cytosol. Cyclin D1 expression was higher in the cytosolic fractions of benign and non-involved than malignant tissues. Furthermore, in malignant tissues, tCho showed a positive correlation with the cytosolic and nuclear expression of β-catenin and cyclin D1 and also a correlation between nuclear expressions of both these proteins was seen. Higher cytosolic β-catenin expression was seen in progesterone receptor negative than positive patients. Results provide an evidence of correlation between non-invasive biomarker, tCho and the Wnt/β-catenin pathway. The findings explain the molecular mechanism of tCho elevation which may facilitate exploration of additional therapeutic targets for breast cancer.

摘要

总胆碱(tCho)被体内 MRS 用于乳腺癌诊断的生物标志物。为了了解乳腺癌中 tCho 升高的分子机制,评估了 tCho 与β-连环蛋白和细胞周期蛋白 D1 的关联。从 20 例恶性、10 例良性和 20 例非受累乳腺组织中分离出 100 个分数。使用 ELISA 估计β-连环蛋白和细胞周期蛋白 D1 的细胞质和核表达。恶性组织中的 tCho 高于良性组织。恶性组织中的细胞质和核β-连环蛋白表达高于良性和非受累组织。在恶性组织中,β-连环蛋白和细胞周期蛋白 D1 的核表达高于细胞质。良性和非受累组织的细胞质分数中的细胞周期蛋白 D1 表达高于恶性组织。此外,在恶性组织中,tCho 与β-连环蛋白和细胞周期蛋白 D1 的细胞质和核表达呈正相关,并且还观察到这两种蛋白质的核表达之间存在相关性。孕激素受体阴性患者的细胞质β-连环蛋白表达高于阳性患者。结果提供了非侵入性生物标志物 tCho 与 Wnt/β-连环蛋白途径之间相关性的证据。这些发现解释了 tCho 升高的分子机制,这可能有助于探索乳腺癌的其他治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a85d/5440410/2d87d088b58b/41598_2017_1459_Fig1_HTML.jpg

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