A Mechanism of Cyclin D1 Action Encoded in the Patterns of Gene Expression in Human Cancer

Cell. 2003 Aug 8;114(3):323-34. doi: 10.1016/s0092-8674(03)00570-1.

Abstract

Here we describe how patterns of gene expression in human tumors have been deconvoluted to reveal a mechanism of action for the cyclin D1 oncogene. Computational analysis of the expression patterns of thousands of genes across hundreds of tumor specimens suggested that a transcription factor, C/EBPbeta/Nf-Il6, participates in the consequences of cyclin D1 overexpression. Functional analyses confirmed the involvement of C/EBPbeta in the regulation of genes affected by cyclin D1 and established this protein as an indispensable effector of a potentially important facet of cyclin D1 biology. This work demonstrates that tumor gene expression databases can be used to study the function of a human oncogene in situ.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • CCAAT-Enhancer-Binding Protein-beta / genetics
  • CCAAT-Enhancer-Binding Protein-beta / metabolism*
  • Cyclin D1 / genetics*
  • Cyclin D1 / metabolism*
  • Databases, Genetic
  • Gene Expression Profiling*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Neoplasms / genetics*
  • Oligonucleotide Array Sequence Analysis
  • Promoter Regions, Genetic
  • Statistics, Nonparametric
  • Tumor Cells, Cultured

Substances

  • CCAAT-Enhancer-Binding Protein-beta
  • Neoplasm Proteins
  • Cyclin D1