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