Defining the Role of Post-Translational Modifications in SRC-3-Mediated Repression of mRNA Translation

Abstract

Breast cancer is the most common, malignant cancer of women in North America; however, there are a number of criteria that determine the prognosis of each cancer. Breast cancer development and progression is influenced by gene expression patterns of both the tumor cells, as well as cells within the tumor microenvironment, such as macrophages. Steroid receptor coactivator 3 (SRC-3) is a molecule that has been shown to influence gene expression both within breast cancer cells and within macrophages. SRC-3 is a potent oncogene in breast cancer cells, functioning as a coactivator of hormone-driven transcription, and a translational repressor of proinflammatory cytokines, such as TNF , in response to lipopolysaccharide (LPS) stimulation of macrophages. I hypothesized that SRC-3 may inhibit tumor-promoting TNF in macrophages activated by paracrine signaling from breast cancer cells, as well; however, our in vitro data do not show any dependence on SRC-3 or its two related proteins, SRC-1 or SRC-2, for macrophage-induced breast cancer cell invasion. Thus, we decided to further characterize the members of the SRC family within breast cancer cells and not macrophages. Our laboratory discovered that an isoform of SRC-3, Delta 4, is a strong inducer of breast cancer cell metastasis, and our preliminary data indicate that it may be a predictor of basal breast carcinomas, the most aggressive type of breast cancer. Additionally, I developed a diagnostic tool for measuring minute amounts of oncogenic SRC-3 within tumor cells. By understanding how different members of the SRC family are expressed during breast cancer, we aim to create tools for personalized medicine, providing tumor-specific targets to be tested for future cancer intervention.

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Document Details

Document Type
Technical Report
Publication Date
Oct 01, 2012
Accession Number
ADA570212

Entities

People

  • Amber Johnson

Organizations

  • Baylor College of Medicine

Tags

DTIC Thesaurus Topics

  • Amino Acids
  • Biomedical Research
  • Breast Cancer
  • Cancer
  • Cell Line
  • Cell Membrane Structures
  • Cell Movement
  • Cells
  • Culture Techniques
  • Epithelial Cells
  • Gene Expression
  • Indicator Dyes
  • Mass Spectrometry
  • Molecules
  • Neoplasms
  • Proteins

Fields of Study

  • Biology
  • Medicine

Readers

  • Molecular Genetics
  • Oncology (Cancer Research).