A molecular signature of normal breast epithelial and stromal cells from Li-Fraumeni syndrome mutation carriers. Academic Article uri icon

Overview

MeSH

  • Adolescent
  • Adult
  • Aza Compounds
  • Bicyclo Compounds, Heterocyclic
  • Carcinoma, Ductal, Breast
  • Cells, Cultured
  • Female
  • Gene Expression Profiling
  • Genetic Predisposition to Disease
  • Haploinsufficiency
  • Humans
  • Oligonucleotide Array Sequence Analysis
  • Pyrimidines
  • RNA, Messenger
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Markers, Biological
  • Tumor Suppressor Protein p53

MeSH Major

  • Breast Neoplasms
  • Epithelial Cells
  • Gene Expression Regulation, Neoplastic
  • Germ-Line Mutation
  • Li-Fraumeni Syndrome
  • Neoplasm Proteins
  • Stromal Cells

abstract

  • Specific changes in gene expression during cancer initiation should enable discovery of biomarkers for risk assessment, early detection and targets for chemoprevention. It has been previously demonstrated that altered mRNA and proteome signatures of morphologically normal cells bearing a single inherited "hit" in a tumor suppressor gene parallel many changes observed in the corresponding sporadic cancer. Here, we report on the global gene expression profile of morphologically normal, cultured primary breast epithelial and stromal cells from Li-Fraumeni syndrome (LFS) TP53 mutation carriers. Our analyses identified multiple changes in gene expression in both morphologically normal breast epithelial and stromal cells associated with TP53 haploinsufficiency, as well as interlocking pathways. Notably, a dysregulated p53 signaling pathway was readily detectable. Pharmacological intervention with the p53 rescue compounds CP-31398 and PRIMA-1 provided further evidence in support of the central role of p53 in affecting these changes in LFS cells and treatment for this cancer. Because loss of signaling mediated by TP53 is associated with the development and survival of many human tumors, identification of gene expression profiles in morphologically normal cells that carry "one-hit" p53 mutations may reveal novel biomarkers, enabling the discovery of potential targets for chemoprevention of sporadic tumors as well.

publication date

  • October 2010

has subject area

  • Adolescent
  • Adult
  • Aza Compounds
  • Bicyclo Compounds, Heterocyclic
  • Breast Neoplasms
  • Carcinoma, Ductal, Breast
  • Cells, Cultured
  • Epithelial Cells
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Genetic Predisposition to Disease
  • Germ-Line Mutation
  • Haploinsufficiency
  • Humans
  • Li-Fraumeni Syndrome
  • Neoplasm Proteins
  • Oligonucleotide Array Sequence Analysis
  • Pyrimidines
  • RNA, Messenger
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stromal Cells
  • Tumor Markers, Biological
  • Tumor Suppressor Protein p53

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3039408

PubMed ID

  • 21311097

Additional Document Info

start page

  • 405

end page

  • 422

volume

  • 1

number

  • 6