Homocysteine is an Oncometabolite in Breast Cancer, Which Promotes Tumor Progression and Metastasis
Abstract
The hypothesis in this project is that homocysteine is an oncometabolite in breast cancer. We propose to test this hypothesis with three specific aims: (1) Investigate using two different mouse models of spontaneous breast cancer (MMTV-HRAS mouse and MMTV-PyMT mouse) whether Mthfr is silenced through DNA methylation and as a result the levels of the oncometabolite homocysteine are elevated in tumors; (2) Investigate whether homocysteine promotes breast cancer progression and lung metastasis by comparing the disease process in MMTV-HRAS and MMTV-PyMT mice on two different genetic backgrounds: Mthfr / and Mthfr-/-. Investigate the ability of homocysteine to induce TGF-b, ANGPTL4, and MMP-9 in breast cancer cell lines and to disrupt the barrier function of lung microvascular endothelial cells; (3) Investigate using breast cancer cell lines whether over expression of MTHFR or exposure to N5-methyltetrahydrofolate decreases cell proliferation in vitro and suppresses tumor growth in xenografts in vivo.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2018
- Accession Number
- AD1055786
Entities
People
- Vadivel Ganapathy
Organizations
- Texas Tech University Health Sciences Center