Research Abstract:
Our laboratory is interested in the genetics of breast cancer. We have identified a novel mammary-specific gene, referred to as mammaglobin. Recent investigations indicate that approximately 80 percent of all primary and metastatic breast cancers are mammaglobin positive. Mammaglobin is a secreted protein and mammaglobin has been detected in the sera of breast cancer patients. These properties make mammaglobin an ideal candidate as a clinical marker for breast cancer detection. We are exploring the functional role that mammaglobin may have in breast physiology and we are also studying the molecular mechanisms that mediate this exquisite breast-specific expression.
Another focus of our lab involves the molecular mechanisms that mediate tumor invasion. Our lab has active collaborations with physician/scientists in the Department of Surgery, to better understand the genetic and molecular events that mediate breast cancer metastasis. Working with Dr. Will Gillanders, our laboratory team has shown that siRNA mediated down-regulation of the protein EpCAM, results in a dramatic change in the ability of breast cancer cells to invade. Since EpCAM is up-regulated in the majority of breast cancers, understanding the molecular basis for EpCAM associated tumor cell invasion may lead to new therapeutic strategies in the treatment of breast cancer.
Working with Dr. Rebecca Aft, we have been able to isolate tumor cells from the bone marrow of breast cancer patients. Since it is metastatic breast cancer cells that lead to breast cancer mortality, this work will help elucidate the genetic and molecular events that are critical breast cancer metastasis.
Selected Publications:
Bernstein J, Godbold J, Raptis G, Watson M, Levinson B, Aaronson S, and Fleming T. Identification of Mammaglobin as a Novel Serum Marker for Breast Cancer. Clin Cancer Res 2005 11:6528-6535.
Pethiyagoda CL, Welch DR, Fleming TP. Dipeptidyl peptidase IV (DPPIV) inhibits cellular invasion of melanoma cells. Clin Exp Metastasis 2001 18:391-400.
Watson M, Darrow C, Jensen R, et al. Mammaglobin expression in primary, metastatic, and occult breast cancer. Cancer Res 1999 59:3028-3031.
Watson M, Darrow C, Zimonjic D, et al. Structure and transcriptional regulation of the human mammaglobin gene, a breast cancer associated member of the uteroglobin gene family localized to chromosome 11q13. Oncogene 1998 16:817-824.
Watson M, Fleming T. Mammaglobin, a mammary-specific member of the uteroglobin gene family, is over-expressed in human breast cancer. Cancer Res 1996 56:860-865.
Last Updated: 09/27/2006 |