Sign up for Table of Contents Alerts.

Email this page

Print this page

Report

Inhibition of cyclin D1 gene transcription by Brg-1

Mahadev Rao, Mathew C. Casimiro, Michael P. Lisanti, Mark D'Amico, Chenguang Wang, L. Andrew Shirley, Jennifer E. Leader, Manran Liu, Michael Stallcup, Daniel A. Engel, Daniel J. Murphy and Richard G. Pestell

Purchase article for $19

Subscribe to this journal for $129/year

The evolutionarily conserved SWI-SNF chromatin remodeling complex regulates cellular proliferation. A catalytic subunit, BRG-1, is frequently down regulated, silenced or mutated in malignant cells, however, the mechanism by which BRG-1 may function as a tumor suppressor or block breast cancer cellular proliferation is not understood. The cyclin D1 gene is a collaborative oncogene overexpressed in greater than 50% of human breast cancers. Herein, BRG-1 inhibited DNA synthesis and cyclin D1 expression in human MCF-7 breast cancer epithelial cells. The cyclin D1 promoter AP-1 and CRE sites were required for repression by BRG-1 in promoter assays. BRG-1 deficient cells abolished and siRNA to BRG-1 reduced, formation of the BRG-1 chromatin complex. The endogenous cyclin D1 promoter AP-1 site bound BRG-1. Estradiol treatment of MCF7 cells induced recruitment of BRG-1 to the endogenous hpS2 gene promoter. Estradiol, which induced cyclin D1 abundance, was associated with a reduction in recruitment of the co-repressors HP1α/HDAC1 to the endogenous cyclin D1 promoter AP-1/BRG-1 binding sites. These studies suggest the endogenous cyclin D1 promoter BRG-1 binding site functions as a molecular scaffold in the context of local chromatin upon which coactivators and corepressors are recruited to regulate cyclin D1.

Authors

Mahadev Rao

Kimmel Cancer Center; Philadelphia, PA

Mathew C. Casimiro

Kimmel Cancer Center; Philadelphia, PA

Michael P. Lisanti

Thomas Jefferson University; Philadelphia, PA

Mark D'Amico

Lombardi Cancer Center; Washington D.C.

Chenguang Wang

Kimmel Cancer Center; Philadelphia, PA

L. Andrew Shirley

Kimmel Cancer Center; Philadelphia, PA

Jennifer E. Leader

Kimmel Cancer Center; Philadelphia, PA

Manran Liu

Kimmel Cancer Center; Philadelphia, PA

Michael Stallcup

University of Southern California School of Medicine; Los Angeles, CA

Daniel A. Engel

University of Virginia School of Medicine; Charlottesville, VA

Daniel J. Murphy

University of Virginia School of Medicine; Charlottesville, VA

Richard G. Pestell

Kimmel Cancer Center; Philadelphia, PA

Purchase article for $19

Subscribe to this journal for $129/year