Eukaryotic chromosomes are separated into topologically independent loop domains, anchored onto the nuclear matrix by specific DNA sequences called matrix attachment regions (MARs). Proteins that specifically bind to MARs may be important for the modulation of DNA organization and cell function. Our previously cloned thymocyte-specific MAR-binding protein, SATB1, defines a novel class of DNA-binding proteins that recognize a specific region with the high unwinding capability typically found in MARs. We have recently identified a new MAR-binding protein of 114 kDA (p114) from human breast carcinoma. The MAR-binding activity of p114 was totally undetectable in normal breast tissues and in benign breast lesions. Much higher p114 MAR-binding activity was detected for poorly differentiated carcinomas than for well differentiated carcinomas. p114 has potential as a marker for the early detection of breast carcinomas, and it may also provide a tool to study differences, at a molecular level, between the regulatory mechanisms of malignant and normal cells. We will examine whether p114 MAR-binding activity plays a critical role in the tumorigenic properties of breast cancer cells, using MCF-7 cells as a model. p114 activity will be determined for MCF-7 cells prior to and after estrogen treatment of these cells, as well as for MCF-7 clones transfected with the v-ras(H) oncogene (MCF-7ras) which no longer require estrogen to form tumors in nude mice. For a similar purpose, we will also test p114 activity in the human breast epithelial cell line HBL100 at different passage numbers. The malignant potential of this cell line increases as passage numbers increase. We will study the tumorigenic and possibly metastasizing potential of p114 by transfecting a p114 expression plasmid into human epithelial cells and into the hormone- dependent MCF-7 cells. Information on the breast carcinoma associated MAR-binding protein may be critical for understanding the cause of breast cancer and may be linked to breast tumor therapy in the future.
| Liu, W M; Guerra-Vladusic, F K; Kurakata, S et al. (1999) HMG-I(Y) recognizes base-unpairing regions of matrix attachment sequences and its increased expression is directly linked to metastatic breast cancer phenotype. Cancer Res 59:5695-703 |
