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

Cell 114: 323-334 2003. Published: 2003.08.07

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

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.

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Supplemental Data

Description Link/Filename
Supplementary Information 1 (cyclin D1 nearest neighbors) SI1.txt
full text http://download.cell.com/pdfs/0092-8674/PIIS0092867403005701.pdf
Preview in Cell http://download.cell.com/pdfs/0092-8674/PIIS0092867403006019.pdf
Supplementary Information 2 (GCM KSS) SI2.txt
Nature News and Views http://www.nature.com/cgi-taf/DynaPage.taf?file=/nature/journal/v424/n6951/full/424898a_fs.html&content_filetype=PDF
Supplementary Information 3 (prostate KSS) SI3.txt
Nature Reviews in Cancer Highlights http://www.nature.com/cgi-taf/DynaPage.taf?file=/nrc/journal/v3/n9/full/nrc1175_fs.html&filetype=pdf
Supplementary Information 4 (lung KSS) SI4.txt
Nature Genetics Research Notes http://www.nature.com/cgi-taf/DynaPage.taf?file=/ng/journal/v35/n1/full/ng0903-19.html&filetype=PDF
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