Functional Characteristics of Tumor-Associated Protein Spot14 and Interacting Proteins in Mouse Mammary Epithelial and Breast Cancer Cell Lines

摘要

Thyroid Hormone Responsive Protein Spot14 (S14) is known to be necessary for high rate de novo fatty acid synthesis, and elevated S14 is correlated with reduced disease free survival of women afflicted with breast cancer. The molecular mechanism of S14 remains illusive. Two models exist for S14 function: one implicated with transcriptional events and the other in metabolic processes. These findings suggest that S14 may not directly influence lipogenic gene expression. To that end, exogenous S14 fused to a nuclear localization sequence (NLS) trafficed to the nucleus but did not alter S14 responsive genes ME1 and PCx. Despite the shift toward lipogenesis indicated by Bodipy and NMR, exogenous S14 did not alter glycolytic or lipogenic enzyme levels in normal or ErbB2 tumor cells. A major finding in this report is that glycolytic and lipogenic enzyme abundance was altered in a serum dependent manner for normal but not ErbB2 cells. S14 overexpression in normal CiT3 cells, but in not ErbB2 cells, provided a growth advantage when serum was depleted of lipid and had low glucose. ErbB2 cells did not respond to progestin regardless of S14 overexpression because they lack the progesterone receptor. Together, these results show that S14 does not alter gene expression in these cell culture systems.