Regulatory Control of Breast Tumor Cell Poly (ADP-Ribose) Polymerase
Abstract
We have previously isolated an intact, stable, and fully functional multiprotein DNA replication complex (designated the DNA synthesome) from a variety of non-malignant and malignant tumor cells and tissues including breast cancer cells. We have also shown that poly(ADP-ribose) polymerase (PARP) is among the components of the DNA synthesome. The transformation of a non-malignant human cell to a malignant stat is accompanied by a significant alteration in the mobility of specific components of the DNA synthesome, (such as PCNA) following 2D-PAOE analysis of the DNA synthesome, together with a 4-6-fold decrease in the replication fidelity of the replication complex. In order to establish whether the malignant transformation process is accompanied by an alteration in PARP, we purified PARP from malignant and non-malignant breast cells using phosphocellulose and hydroxylapatite chromatography. PARP was enriched during its purification from these cells. We have also found that PARP isolated from malignant breast cells exhibits a different migration pattem, when analyzed by 2D-PAGE, compared to the enzyme isolated from non-malignant breast cells; indicating that this enzyme may be modified in breast cancer cells. Mass spectrometric analyses and physical characteristics determination of PARP from malignant and non-malignant breast cells are underway in order to explain how PARP modification may contribute to the observed decrease in replication fidelity in breast cancer cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2003
- Accession Number
- ADA421036
Entities
People
- Linda Milkas
- Waleed Abdel-aziz
Organizations
- University of Maryland, Baltimore