| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Endocrinology |
1 Department of Systems Biology, Harvard Medical School; 2 Division of Molecular and Cellular Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute; and 3 Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
Requests for reprints: Myles Brown, Division of Molecular and Cellular Oncology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115. Phone: 617-632-3948; Fax: 617-582-8501; E-mail: myles_brown{at}dfci.harvard.edu.
Estrogen receptor
(ER
) mediates breast cancer proliferation through transcriptional mechanisms involving the recruitment of specific coregulator complexes to the promoters of cell cycle genes. The coactivator-associated arginine methyltransferase CARM1 is a positive regulator of ER
-mediated transcriptional activation. Here, we show that CARM1 is essential for estrogen-induced cell cycle progression in the MCF-7 breast cancer cell line. CARM1 is specifically required for the estrogen-induced expression of the critical cell cycle transcriptional regulator E2F1 whereas estrogen stimulation of cyclin D1 is CARM1 independent. Upon estrogen stimulation, the E2F1 promoter is subject to CARM1-dependent dimethylation on histone H3 arginine 17 (H3R17me2) in a process that parallels the recruitment of ER
. Additionally, we find that the recruitment of CARM1 and subsequent histone arginine dimethylation are dependent on the presence of the oncogenic coactivator AIB1. Thus, CARM1 is a critical factor in the pathway of estrogen-stimulated breast cancer growth downstream of ER
and AIB1 and upstream of the cell cycle regulatory transcription factor E2F1. These studies identify CARM1 as a potential new target in the treatment of estrogen-dependent breast cancer. [Cancer Res 2008;68(1):301–6]
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |