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

Project

Transcriptional Regulation

Additional Projects/
Categories

Bioinformatics & Computational Biology

Abstract

Here we describe how patterns of gene expression in human tumors have been deconvoluted to reveal a previously unappreciated 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/EBPβ/Nf-Il6, participates in the consequences of cyclin D1 overexpression. Functional analyses confirmed the involvement of C/EBPβ 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.

Authors

Justin Lamb, Sridhar Ramaswamy, Heide L. Ford, Bernardo Contreras, Robert V. Martinez, Frances S. Kittrell, Cynthia A. Zahnow, Nick Patterson, Todd R. Golub and Mark E. Ewen

Publication Date

08/08/2003

Contact emails

mark_ewen@dfci.harvard.edu
justin@genome.wi.mit.edu

Citation

Cell 114: 323-334 2003

Supplemental Information

URLs

Name	URL
full text	http://download.cell.com/pdfs/0092-8674/PIIS0092867403005701.pdf
Preview in Cell	http://download.cell.com/pdfs/0092-8674/PIIS0092867403006019.pdf
Nature News and Views	http://www.nature.com/cgi-taf/DynaPage.taf?file=/nature/journal/v424/n6951/full/424898a_fs.html&content_filetype=PDF
Nature Reviews in Cancer Highlights	http://www.nature.com/cgi-taf/DynaPage.taf?file=/nrc/journal/v3/n9/full/nrc1175_fs.html&filetype=pdf
Nature Genetics Research Notes	http://www.nature.com/cgi-taf/DynaPage.taf?file=/ng/journal/v35/n1/full/ng0903-19.html&filetype=PDF

Files

Description	File
Supplementary Information 1 (cyclin D1 nearest neighbors)	SI1.txt
Supplementary Information 2 (GCM KSS)	SI2.txt
Supplementary Information 3 (prostate KSS)	SI3.txt
Supplementary Information 4 (lung KSS)	SI4.txt
Supplementary Information 5 (brain KSS)	SI5.txt
Supplementary Information 6 (NCI60 KSS)	SI6.txt
Supplementary Information 7 (chromosome coordinates)	SI7.pdf
Supplementary Information 8 (competitor oligonucleotides)	SI8.pdf
Supplementary Information 9 (additional panels for Figure 6D)	SI9.pdf
Supplementary Information 10 (additional panels for Figure 6E)	SI10.pdf
raw gene expression data	raw_data.res