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

• Published in: Scientific reports 2017-05, Vol.7 (1), p.2221-11, Article 2221
• Main Authors: Agarwal, Khushbu, Hariprasad, Gururao, Rani, Komal, Sharma, Uma, Mathur, Sandeep R., Seenu, Vurthaluru, Parshad, Rajinder, Jagannathan, Naranamangalam R.
• Format: Article
• Language: English
• Subjects: 140/131; 631/67/1347; 692/4028/67/1347; 82; 82/80; Adult; Aged; Benign; beta Catenin - genetics; beta Catenin - metabolism; Breast cancer; Breast Neoplasms - diagnosis; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Choline; Choline - genetics; Choline - metabolism; Cyclin D1; Cyclin D1 - genetics; Cytosol; Enzyme-Linked Immunosorbent Assay; Female; Gene Expression; Humanities and Social Sciences; Humans; Magnetic Resonance Spectroscopy; Mammography; Middle Aged; Models, Biological; Molecular modelling; multidisciplinary; Neoplasm Staging; Nuclei; Pilot Projects; Progesterone; Receptors, Cell Surface - metabolism; Science; Science (multidisciplinary); Signal Transduction; Spectroscopy; Tissues; Wnt protein; β-Catenin
• ISSN: 2045-2322; 2045-2322
• 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.