AACR Distinguished Lectureship in Breast Cancer Research

Supported by Bristol-Myers Squibb, this AACR lectureship has been established to recognize outstanding science that has inspired or has the potential to inspire new perspectives on the etiology, diagnosis, treatment, or prevention of breast cancer.

This lectureship is selected by the San Antonio Breast Cancer Symposium Program Committee, and is not open to nomination.

Dr. Joan S. Brugge delivered her award lecture entitled, Protective Adaptive Responses to Breast Cancer Therapies, during  the 34th Annual CTRC-AACR San Antonio Breast Cancer Symposium in San Antonio, TX. The award ceremony and lecture were held Wednesday, December 7, 11:30 a.m. in Exhibit Hall D.

• Learn more about the San Antonio Breast Cancer Symposium and the Award Lecture.

The American Association for Cancer Research honors Dr. Joan S. Brugge with 2011 AACR Distinguished Lectureship in Breast Cancer Research.

Dr. Brugge has been a pioneer and a major leader in the field of Cell Biology and Cancer Research. Her research accomplishments include many seminal contributions that have provided critical insights into an understanding of the processes involved in oncogenesis and the normal functions of proto-oncogenes. Dr. Brugge first demonstrated that SV40 large T antigen is required for maintenance of the transformed state. This seminal work was important in formulating hypotheses regarding the activity of dominant oncogenes and is the basis for the use of temperature-sensitive mutants of T antigen as tools for reversible cell immortalization and transformation. As a postdoctoral fellow, Dr. Brugge first identified the product of the Rous sarcoma virus v-Src protein. This work represented the first identification of a retroviral oncogene product and made it possible to perform studies to elucidate the mechanism of oncogenic transformation of RSV and the function of this protein in normal cells. Inhibitors of the Src protein are not in clinical trials for cancer.

In work begun with Raymond Erikson, but completed after she joined the Faculty at the State University of New York at StonyBrook, Dr. Brugge identified two protein chaperones that associated with Src and showed that one of these, hsp90, is involved in processing the Src protein. This work represented the first study characterizing the interactions of an intracellular protein with chaperone proteins and contributed to early concepts of hsp proteins as protein chaperones. Inhibitors of hsp90 are now in clinical trials for cancer.

While at Stonybrook, Dr. Brugge collaboratively showed that the interaction of c-Src with polyoma virus middle T antigen significantly activates c-Src kinase activity, thus providing a mechanism whereby middle T could manipulate the activity of a cellular proto-oncogene product, leading to oncogenic transformation. Dr. Brugge’s laboratory first showed that the protooncogene, Ras is required for Erk/MAPKinase activation by growth factors, providing the first clue regarding the cellular pathway that regulates Erk, a key integrator of many cellular responses to hormones and growth factors.

More recently, her laboratory has utilized a 3D model for mammary morphogenesis to investigate the cellular pathways and processes associated with early stages of tumorigenesis in structures that share properties with glandular acini in vivo. These studies have defined events involved in morphogenesis from a single epithelial cell to a hollow, growth arrested spheroid structure, demonstrated the utility of this culture system in modeling processes that take place during tumorigenesis, and elucidated mechanisms involved in several different phenotypic transformations.

Dr. Brugge's laboratory has used this model to define that the nature of cell death caused by loss of anchorage to extracellular matrix  and defined  mechanisms whereby oncogenes induce anchorage independence. These studies revealed a critical role for matrix attachment in regulating the metabolic activity of cells and indicated that oncogenes that promote anchorage independence need to prevent apoptosis and rescue the metabolic defects associated with loss of matrix attachment.

Her laboratory has also discovered a totally new mechanism of cell death caused by matrix detachment – entosis, where loss of matrix changes the dynamics of cell-cell compaction allowing one cell to internalized by another. Cell-in-cell structures have been described for decades by pathologists (particularly involving tumor cells in fluid exudates),  but there was no understanding of how cells were internalized into others. These studies provided an interesting mechanistic understanding of this process.

Dr. Brugge joined the faculty of the Department of Cell Biology at Harvard Medical School in July 1997, and became the Chair of this department in 2004. A graduate of Northwestern University, she received her PhD from the Baylor College of Medicine. Dr. Brugge has held full professorships at the State University of New York, Stony Brook, and the University of Pennsylvania, where she was also named as an investigator at the Howard Hughes Medical Institute.