Eliot M Rosen

Title

Professor

Department

Breast Cancer
Research

Research

Dr. Rosen has devoted a number of years to studies of the molecular functions of the breast cancer susceptibility gene BRCA1, including its roles in regulating hormonal response pathways (estrogen and progesterone receptors), gene transcription, the response to DNA damage, and progression through the cell cycle. As an outgrowth of his longstanding interest in BRCA1, Dr. Rosen has developed an interest in the molecular function of a second breast cancer susceptibility, BRCA2, which is also linked to an increased incidence of prostate cancer; and the BRCA1 and BRCA2 genes have overlapping but not identical functions. Relative to the interest in BRCA gene function in cancer, we have recently been investigating the role of BRCA1 (and now BRCA2) as targets for the cancer prevention agents indole-3-carbinol, diindolylmethane (DIM, a major metabolite of indole-3-carbinol), and genistein. We have demonstrated that these genes are up-regulated by indole-3-carbinol and genistein in several hormonally-responsive cancer cell types, including breast cancer cells. Thus, a significant focus on our work is on chemoprevention.

As a result of a number of years of study of the mechanism by which BRCA1 interacts with the estrogen receptor and inhibits its activity, he and a colleague (Dr. York Tomita) have developed a three-dimensional molecular model for the BRCA1: estrogen receptor interaction. This model has allowed us to identify novel small molecule compounds that mimic a critical aspect of the BRCA1: ER interaction; and we have validated the ability of several of these novel compounds to inhibit estrogen receptor activity in breast cancer cells. The further development of these compounds for potential usage in breast cancer prevention or treatment is a current interest of the Rosen laboratory.

Dr. Rosen's other major interest is in scatter factor/hepatocyte growth factor-c-Met signaling pathways, particularly related to protection of breast cancer, prostate cancer, and malignant glioma (brain tumor) cells against cytotoxicity and apoptosis induced by DNA damaging agents of the type used in cancer treatment (radiation therapy and ceratin cancer chemotherapy drugs) and death receptor ligands such as TRAIL (the TNF-related apoptosis inducing ligand, which is a proposed cancer treatment agent). He has made a number of significant contributions in this field of research.