US EPA

4532785 

Journal Article 

Homocysteine Is an Oncometabolite in Breast Cancer, Which Promotes Tumor Progression and Metastasis 

Ganapathy, V 

2017 

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-beta, 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 grow thin xenografts in vivo.