S14 as a Therapeutic Target in Breast Cancer
Abstract
This project aims to determine the importance of "S14", a nuclear protein that signals for lipid synthesis, in breast cancer. Our aims are first to develop a model of anti-S14 breast cancer therapy in mice. Intratumoral adenoviral delivery of an S14-antisense gene into human breast cancer cell xenografts significantly inhibited tumor growth, and we verified the specificity of this effect using siRNA. We identified two siRNAs that knockdown S14 protein in breast cancer cells, and find that they are cytotoxic. Second, to define the structure of the S14 multimer by X-ray crystallography S14 is very difficult to crystallize. We have now used circular dichroism, NMR, and computer modeling to discern the structure of the S14 tetramerization domain. Third, to define the utility of S14 as a clinical marker. We produced monoclonal S14 antibodies for an immunohistochemical study of 131 breast cancer cases. This revealed strong associations of S14 staining with invasive tumor size and grade, and a striking power to predict tumor recurrence. Importantly, S14 expression scores did not correlate with those for sex steroid receptors or Her2/neu. Thus, S14 is a driver and a marker of virulent breast cancer that uniquely identifies cases that are likely to recur.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2005
- Accession Number
- ADA442981
Entities
People
- William Kinlaw
Organizations
- Dartmouth College