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PMID: 20133671 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

MYC regulation of a "poor-prognosis" metastatic cancer cell state.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 107 ·No. 8 ·2010-02-23 ·Pages 3698-703

Wolfer A, Wittner BS, Irimia D, Flavin RJ, Lupien M, Gunawardane RN, Meyer CA, Lightcap ES, Tamayo P, Mesirov JP, Liu XS, Shioda T, Toner M, Loda M, Brown M, Brugge JS, Ramaswamy S

Abstract

Gene expression signatures are used in the clinic as prognostic tools to determine the risk of individual patients with localized breast tumors developing distant metastasis. We lack a clear understanding, however, of whether these correlative biomarkers link to a common biological network that regulates metastasis. We find that the c-MYC oncoprotein coordinately regulates the expression of 13 different "poor-outcome" cancer signatures. In addition, functional inactivation of MYC in human breast cancer cells specifically inhibits distant metastasis in vivo and invasive behavior in vitro of these cells. These results suggest that MYC oncogene activity (as marked by "poor-prognosis" signature expression) may be necessary for the translocation of poor-outcome human breast tumors to distant sites.

MeSH Terms
Biomarkers, Tumor/genetics Breast Neoplasms/genetics,pathology Cell Movement/genetics Female Gene Expression Profiling Gene Expression Regulation, Neoplastic Humans Neoplasm Metastasis Oligonucleotide Array Sequence Analysis Prognosis Proto-Oncogene Proteins c-myc/metabolism
Chemicals
Biomarkers, Tumor Proto-Oncogene Proteins c-myc
Authors & Affiliations
17 authors, click to expand affiliations / ORCID
Wolfer Anita
Massachusetts General Hospital Cancer Center, Boston, MA 02114, USA.
Wittner Ben S
Irimia Daniel
Flavin Richard J
Lupien Mathieu
Gunawardane Ruwanthi N
Meyer Clifford A
Lightcap Eric S
Tamayo Pablo
Mesirov Jill P
Liu X Shirley
Shioda Toshi
Toner Mehmet
Loda Massimo
Brown Myles
Brugge Joan S
Ramaswamy Sridhar
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
1091-6490
DOI
10.1073/pnas.0914203107
Published
2010-02-23
Epub
2010-00-04
Pages
3698-703
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC2840447
Subset
IM
Grants
NCI NIH HHS · K08 CA100339-06 · United States
NCI NIH HHS · P50 CA089393 · United States
NCI NIH HHS · R21 CA135601 · United States
NCI NIH HHS · P50 CA89393 · United States
NCI NIH HHS · K08 CA100339 · United States
NIBIB NIH HHS · P41 EB002503 · United States
External Links
PubMed source DOI: 10.1073/pnas.0914203107 PMC Full Text View journal details
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