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Patricia A. D'Amore, PhD, MBA

Professor, Department of Pathology, Harvard Medical School

Charles L. Schepens Professor of Ophthalmology, Department of Ophthalmology, Harvard Medical School

Research Associate, Vascular Biology Program, Boston Children's Hospital

Co-Director of Research, Sr. Scientist, Ophthalmology, Schepens Eye Research Institute

Contact Info

Patricia D'Amore
Schepens Eye Research Institute
20 Staniford Street

Boston, MA, 02114
Mailstop: Schepens Eye Research
Phone: 617-912-2559
Fax: 617-912-0128
patricia.damore@schepens.harvard.edu

Assistant

Christine Bagley
Administrative Coordinator
Ophthalmology
Schepens Eye Research Institute
20 Staniford Street
3rd Flr.
Boston, MA, 02114
Phone: 617-912-2560
Fax: 617-912-0128
christine.bagley@schepens.harvard.edu

DF/HCC Program Affiliation

Angiogenesis, Invasion and Metastasis
Breast Cancer

DF/HCC Associations

Member, Center Scientific Council

Research Abstract

The frizzled are a family of seven membrane spanning proteins that act as receptors for the Wnts. The Wnts are a family of seareted glycoproteins that have a wide range of roles from axis polarity in Xenopus to tissue differentiation. By differential display, we have identified and cloned a gene that encodes for a protein (which we call FrzA) that is homologous to the extra cellular domain of the frizzled receptor. Functional studies in Xenopus, as well as biochemical analysis in vitro, indicate that FrzA can associate with Wnts and antagonize their actions. FrzA is highly expressed in differentiated, non-proliferating vascular endothelium and a variety of epithelium. We, therefore, examined FrzA expression by in situ hybridization in normal human breast tissue and in mammary tumor tissues. Normal human mammary epithelium and myoepithelium express high levels of FrzA mRNA. FrzA expression is lost in mammary epithelium of ductal carcinoma in situ (DCIS) but remains elevated in the
myopethelium. Invasive mammary carcinoma has no FrzA mRNA expression. Similarly, vascular endothelium of non-proliferating vessels express high levels of FrzA mRNA whereas endothelial cells proliferating in culture have greatly reduced or no FrzA mRNA expression. Wnt-1 has been reported to play a role in mammary tumorigenesis. In fact, the first Wnt family members were originally identified as the protooncogene site of insertion of the mouse mammary tumor virus and was called Int-1. Taken together, the implied role of Wnts in mammary tumorigenesis and the expression pattern of FrzA in breast tumors points to a possible role for FrzA in regulation mammary epithelial cell proliferation and differentiation. We are using
tissue culture models of mammary epithelial differentiation to test this hypothesis.

Publications

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