A mechanism of cyclin D1 action encoded in the patterns of gene expression in human cancer.
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.
Lamb
Justin
J
Departments of Medical Oncology and Medicine, Dana-Farber Cancer Institute and Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA.
Ramaswamy
Sridhar
S
Ford
Heide L
HL
Contreras
Bernardo
B
Martinez
Robert V
RV
Kittrell
Frances S
FS
Zahnow
Cynthia A
CA
Patterson
Nick
N
Golub
Todd R
TR
Ewen
Mark E
ME
D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000378:metabolism*; D019938:Cyclin D1 / Q000235:genetics* / Q000378:metabolism*; D030541:Databases, Genetic; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D018709:Statistics, Nonparametric; D014407:Tumor Cells, Cultured
D022782:CCAAT-Enhancer-Binding Protein-beta; D009363:Neoplasm Proteins; D019938:Cyclin D1