Title

SWI/SNF chromatin remodeling enzyme ATPases promote cell proliferation in normal mammary epithelial cells

UMMS Affiliation

Department of Cell Biology

Date

6-25-2010

Document Type

Article

Medical Subject Headings

Adenosine Triphosphatases; Basement Membrane; Cell Cycle; Cell Line; Cell Proliferation; *Chromatin Assembly and Disassembly; DNA Helicases; Doxycycline; Epithelial Cells; Female; Gene Knockdown Techniques; Humans; Mammary Glands, Human; Nuclear Proteins; Protein Subunits; RNA, Small Interfering; RNA, Small Nucleolar; Transcription Factors; Up-Regulation

Disciplines

Cell Biology

Abstract

The ATPase subunits of the SWI/SNF chromatin remodeling enzymes, Brahma (BRM) and Brahma-related gene 1 (BRG1), can induce cell cycle arrest in BRM and BRG1 deficient tumor cell lines, and mice heterozygous for Brg1 are pre-disposed to breast tumors, implicating loss of BRG1 as a mechanism for unregulated cell proliferation. To test the hypothesis that loss of BRG1 can contribute to breast cancer, we utilized RNA interference to reduce the amounts of BRM or BRG1 protein in the nonmalignant mammary epithelial cell line, MCF-10A. When grown in reconstituted basement membrane (rBM), these cells develop into acini that resemble the lobes of normal breast tissue. Contrary to expectations, knockdown of either BRM or BRG1 resulted in an inhibition of cell proliferation in monolayer cultures. This inhibition was strikingly enhanced in three-dimensional rBM culture, although some BRM-depleted cells were later able to resume proliferation. Cells did not arrest in any specific stage of the cell cycle; instead, the cell cycle length increased by approximately 50%. Thus, SWI/SNF ATPases promote cell cycle progression in nonmalignant mammary epithelial cells.

Rights and Permissions

Citation: J Cell Physiol. 2010 Jun;223(3):667-78. Link to article on publisher's site

Related Resources

Link to Article in PubMed

PubMed ID

20333683