Alteration in the Nuclear Structure of Breast Cancer Cells in Response to ECM Signaling
Abstract
Eukaryotic chromosomes are thought to be separated into topologically independent loop domains by periodic attachment onto an intranuclear frame known as the nuclear matrix. Specific DNA sequences that bind to the nuclear matrix are called matrix attachment regions (MARs), in which a specialized DNA context sequences exhibiting high base unpairing propensity (BUR) is typically found. Besides organization of eukaryotic DNA, BURs/MARs may also be important for various functions including replication, transcription and recombination. A strong BUR-binding protein, pll4, previously isolated from breast carcinoma cells, was identified as to be poly ADP-ribose polymerase (PARP). Depleting PARP by antisense construct in MDA-MB-23 1 cells resulted in the lost of aggressive phenotype in vitro, suggesting a critical role for PARP in the onset and/or maintenance of the malignant phenotype. Additionally, HMG 1(Y) was also found to be BUR-binding protein, and its expression was well correlated with aggressive breast cancer cells. Using three directly comparable cell systems, we demonstrated that the level of HMG 1(Y) expression is dynamically regulated in human breast cancer cells in response to varying types of signaling that affect metastatic ability, including the HRG-erbB pathway and those from extracellular matrix (ECM). Finally, to investigate changes in loop domain structure upon three-dimensional alveolar formation induced by ECM, beta-casein gene was chosen here for future study.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1999
- Accession Number
- ADA385940
Entities
People
- Wen-man Liu
Organizations
- University of California, Berkeley