Functional Characteristics of Tumor Associated Protein Spot14 and Interacting Proteins in Mouse Mammary Epithelial and Breast Cancer Cell Lines
Abstract
Thyroid Hormone Responsive Protein Spot14 (S14) is necessary for high rate de novo fatty acid synthesis. 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 suggesting transcriptional events and the other in metabolic processes. Our previous findings showed that S14 does not alter lipogenic gene expression in the cell lines investigated even if driven to the nucleus. S14 overexpression did not affect glycolytic or lipogenic enzyme levels in normal or ErbB2 tumor cells. However, S14 overexpression enhanced accumulation of total lipids evaluated by Bodipy staining and NMR analysis. 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. We found that mouse ErbB2 cells do not respond to progestin to induce S14 because they lack the progesterone receptor (PR). In contrast, S14 was sharply induced along with FASN by progestin in T47D human breast cancer cells known to express PR. Progestin stimulated total lipid accumulation and increased total fatty acids in T47D cells. Importantly, 13C(U) glucose tracer studies showed a progestin dependent increase of 13C incorporation into de novo palmitate. Together, these results show that S14 does not alter gene expression but functions to enhance the de novo fatty acid synthesis pathway in a progestin dependent way.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2012
- Accession Number
- ADA560835
Entities
People
- Michael C. Rudolph
Organizations
- University of Colorado Health