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PMID: 11158583 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Defective repression of c-myc in breast cancer cells: A loss at the core of the transforming growth factor beta growth arrest program.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 98 ·No. 3 ·2001-01-30 ·Pages 992-9

Chen CR, Kang Y, Massagué J

Abstract

Loss of growth inhibitory responses to the cytokine transforming growth factor beta (TGF-beta) in cancer cells may result from mutational inactivation of TGF-beta receptors or their signal transducers, the Smad transcription factors. In breast cancer, however, loss of TGF-beta growth inhibition often occurs without a loss of these signaling components. A genome-wide analysis of rapid TGF-beta gene responses in MCF-10A human mammary epithelial cells and MDA-MB-231 breast cancer cells shows that c-myc repression, a response that is key to the TGF-beta program of cell cycle arrest, is selectively lost in the cancer cell line. Transformation of MCF-10A cells with c-Ha-ras and c-erbB2 oncogenes also led to a selective loss of c-myc repression and cell cycle arrest response. TGF-beta stimulation of epithelial cells rapidly induces the formation of a Smad complex that specifically recognizes a TGF-beta inhibitory element in the c-myc promoter. Formation of this complex is deficient in the oncogenically transformed breast cells. These results suggest that a Smad complex that specifically mediates c-myc repression is a target of oncogenic signals in breast cancer.

MeSH Terms
Base Sequence Breast Breast Neoplasms/genetics,pathology Cell Cycle/drug effects Epithelial Cells/cytology,drug effects,physiology Female Gene Expression Regulation Gene Expression Regulation, Neoplastic Genes, myc Humans Molecular Sequence Data Proto-Oncogene Proteins c-myc/metabolism Transcription, Genetic Transforming Growth Factor beta/genetics,pharmacology Tumor Cells, Cultured
Chemicals
Proto-Oncogene Proteins c-myc Transforming Growth Factor beta
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Chen C R
Cell Biology Program, Memorial Sloan-Kettering Cancer Center and Howard Hughes Medical Institute, New York, NY 10021, USA.
Kang Y
Massagué J
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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
0027-8424
DOI
10.1073/pnas.98.3.992
Published
2001-01-30
Pages
992-9
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC14697
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.98.3.992 PMC Full Text View journal details
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