Defective repression of c-myc in breast cancer cells: A loss at the core of the transforming growth factor β growth arrest program Journal Article
| Authors: | Chen, C. R.; Kang, Y.; Massagué, J. |
| Article Title: | Defective repression of c-myc in breast cancer cells: A loss at the core of the transforming growth factor β growth arrest program |
| Abstract: | Loss of growth inhibitory responses to the cytokine transforming growth factor β (tgf-β) in cancer cells may result from mutational inactivation of Tgf-β receptors or their signal transducers, the Smad transcription factors. In breast cancer, however, loss of Tgf-β growth inhibition often occurs without a loss of these signaling components. A genome-wide analysis of rapid Tgf-β gene responses in Mcf-1oa human mammary epithelial cells and Mda-mb-231 breast cancer cells shows that c-myc repression, a response that is key to the Tgf-β program of cell cycle arrest, is selectively lost in the cancer cell line. Transformation of Mcf-1oa 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-β stimulation of epithelial cells rapidly induces the formation of a Smad complex that specifically recognizes a Tgf-β 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. |
| Keywords: | signal transduction; controlled study; gene mutation; human cell; promoter region; cell cycle; complex formation; breast cancer; breast; smad protein; transforming growth factor beta; transcription factor; transcription, genetic; cancer cell culture; tumor cells, cultured; breast neoplasms; gene expression regulation; cancer inhibition; gene expression regulation, neoplastic; cytokine; molecular sequence data; cell transformation; nucleotide sequence; genes, myc; gene repression; transforming growth factor beta receptor; epithelial cells; base sequence; genome; oncogene c myc; proto-oncogene proteins c-myc; oncogene ras; oncogene neu; mitosis inhibition; humans; human; female; priority journal; article |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 98 |
| Issue: | 3 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 2001-01-30 |
| Start Page: | 992 |
| End Page: | 999 |
| Language: | English |
| DOI: | 10.1073/pnas.98.3.992 |
| PUBMED: | 11158583 |
| PROVIDER: | scopus |
| PMCID: | PMC14697 |
| DOI/URL: | |
| Notes: | Export Date: 21 May 2015 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work