Id-1 Expression During Breast Cancer Progression

Institution: California Pacific Medical Center Research Institute
Investigator(s): Pierre-Yves Desprez, Ph.D. -
Award Cycle: 1999 (Cycle V) Grant #: 5IB-0111 Award: $78,031
Award Type: IDEA
Research Priorities
Biology of the Breast Cell>Pathogenesis: understanding the disease

Initial Award Abstract (1999)
Breast cancer cells often penetrate the surrounding tissue and eventually metastasize to other body sites. Metastasis is the hallmark of aggressive cancer and normally indicates poor prognosis. Recently, we have found that a specific protein, called Id-1, is associated with mammary epithelial cell phenotypes and accounts for some of the differences between normal and cancerous breast cells in culture. Id-1 is a regulator of a group of gene expression proteins, called transcription factors. The goal of this proposed research is to provide insights into how some of the metastases arise by evaluating the expression of Id-1 in breast cancer biopsies.

We have shown that Id-1 is capable of regulating various aspects of the normal breast function, and we have found that Id-1 protein level has to be tightly regulated in order for the breast cells to properly respond to the signal for growth or gain of milk-producing functions. When such regulation is altered by artificially maintaining a high level of Id-1, cells can no longer respond to the signal for milk production. Additionally, these cells now acquire the ability to break away from each other and dissolve big molecules in their surrounding environment, an invasive property characteristic of aggressive breast cancer cells. To dissolve big molecules, certain enzymes are required. We have identified a novel enzyme, which we call the 120 kD gelatinase, whose production is tightly associated with Id-1 protein, and shown it may be responsible for the ability of breast cells to become invasive. In this project we plan to expand our studies to breast tumor samples using both microscopy and molecular biology techniques to detect and measure the amount of both Id-1 and the 120 kD gelatinase, from biopsy and urine respectively, from the patients.

Since breast cancer is a very heterogeneous disease, biologically and clinically, we hope to find a new marker that indicates the progression of some breast cancers on their way towards their final, untreatable stages. This research will also help to provide a valuable target for treatment of aggressive breast cancers.

Final Report (2001)
In this project we expanded our studies to breast tumor samples using both microscopy and molecular biology techniques to detect and measure the amount of both Id-1 and a novel 120 kDa gelatinase that are believed to be associated with breast tumor migration. We obtained the samples from physicians and pathologists at California Pacific Medical Center. Concerning the potential detection in the urine of gelatinases secreted by the tumor cells, the data were difficult to interpret due to the high levels of secretion of these enzymes by the blood cells. Thus, the analysis of urine samples did not reveal the presence of the 120 kDa gelatinase distinct from already known proteases secreted by other cells. In contrast, the Id-1 data regarding the breast tumor samples were quite clear. We studied tumor samples collected from DCIS and breast tumor grades 1-3. Tissue samples were prepared from immunohistochemistry (IHC) and 'stained' using a commercial antibody specific for Id-1. The DCIS and Grade 1 samples were mostly negative for the presence of Id-1, but the more invasive Grade 2 and 3 samples were positive for Id-1 >50% of the time. This shows that Id-1 could be a useful biomarker of breast cancer progression and potential for invasion of surrounding tissues leading to metastasis.