Department of Pharmacology and Therapeutics
Roswell Park Cancer Institute
Elm and Carlton Streets
Buffalo NY USA 14263
Tel: 716 - 845 - 2356
Fax: 716 - 845 - 5865
E-mail: margot.ip@roswellpark.org

Dr. Margot Ip joined the staff of Roswell Park Cancer Institute (RPCI) in 1976 and was promoted to Member of the Department of Pharmacology & Therapeutics in 1985. She also serves as a Professor in the Molecular Pharmacology & Cancer Therapeutics Program, Roswell Park Graduate Division, University at Buffalo (UB).

Dr. Ip earned her doctoral degree in Biochemistry in 1972 at the University of Wisconsin (UW), Madison, WI. She completed postdoctoral fellowships in the Department of Nutritional Sciences, UW (1973); the Department of Pharmacology, Upstate Medical Center, Syracuse, NY (1975); and the Department of Experimental Therapeutics, RPCI (1976).

Dr. Ip’s research interests include the role of growth factors in breast cancer development and progression, as well as chemopreventive strategies for breast cancer, with focus on conjugated linoleic acid.

Dr. Ip has served as a member of two National Institutes of Health grant review study sections, and serves as an ad hoc grant reviewer for, among others, the NIH and the Department of Defense Breast Cancer Research Program.

Dr. Ip has authored or co-authored more than 200 journal publications, book chapters and abstracts, and is a reviewer for several scientific journals.

Program Overview

The focus of this laboratory is on the identification and characterization of specific pathways regulating the growth of normal and malignant mammary epithelium, with the overall objective of elucidating pathways which may be altered during the development of breast cancer, and/or which may be targeted for therapy or chemoprevention.

Current Programs

A. Proliferative role of tumor necrosis factor (TNF) in normal and malignant breast epithelium

Tumor necrosis factor-alpha (TNF) is a pleiotropic cytokine which we have shown to be a multifunctional regulator of normal postnatal mammary gland development.  Current efforts in the laboratory are devoted to a determination of whether tumor necrosis factor (TNF), which stimulates the growth and morphological development of normal mammary epithelial cells, as well as mammary tumor cells in primary culture, may act in an autocrine or paracrine manner to stimulate the growth of breast tumors, and if so to design therapeutic strategies to counteract this activity. A major part of these studies involves a determination of the signal transduction pathways by which TNF exerts its effects in primary cultures of normal and malignant breast epithelial cells, so that potential therapeutic targets can be identified. Additionally, TNF null mice, as well as mice lacking specific TNF downstream effectors, are being used as tools to determine the biological and molecular events that are altered and mediated, respectively, by TNF in the mammary gland.  TNF null mice are also being used to determine whether TNF plays a stimulatory role in mammary tumorigenesis in mice which overexpress her2/erbB2 in the mammary epithelium.

B. Chemoprevention of breast cancer with conjugated linoleic acid

Our previous studies demonstrated that conjugated linoleic acid (CLA), a family of C18 fatty acids with conjugated double bonds, inhibits rat mammary carcinogenesis and angiogenesis. The naturally occurring c9,t11-CLA isomer, as well as the t10,c12-CLA isomer which is a component of synthetic CLA mixtures, were equally effective. Unexpectedly, in recent studies using a clinically relevant breast cancer model, namely transgenic mice overexpressing her2/erbB2 in the mammary epithelium, we found that t10,c12-CLA accelerated mammary tumorigenesis and stimulated lung metastasis. Dietary supplementation with this isomer was also shown to dramatically alter the mouse mammary stroma. Current studies in the laboratory are focused on a determination of the biological and molecular mechanisms by which each of the CLA isomers exert its effects, with the goal of understanding the opposite effects of the isomers in different mammary tumor models.

Key Publications

Mammary gland biology

D. Zangani, K.M. Darcy, P.A. Masso-Welch, E.S. Bellamy, M.S. Desole and M.M. Ip.  (1999)  Multiple differentiation pathways of mammary stromal cells in vitro: acquisition of a fibroblast, adipocyte or endothelial phenotype is dependent on hormonal and extracellular matrix stimulation.  Differentiation 64: 91-101.

Methods in Mammary Gland Biology and Breast Cancer Research (2000). Editors: M.M. Ip and B.A. Asch. Kluwer Academic/Plenum Press, New York. 

An Histology Atlas of the Rodent Mammary Gland and Human Breast during Normal Postnatal Development and in Cancer (2000). Editors: M.M. Ip and B.A. Asch. Journal of Mammary Gland Biology and Neoplasia Volume 5, #2, April 2000

TNF project

L.M. Varela and M. M. Ip (1996) Tumor necrosis factor-a: a multifunctional regulator of mammary gland development. Endocrinology. 137: 4915-4924. 

P.-P.H. Lee, J.-J. Hwang, G. Murphy and M.M. Ip. (2000) Functional significance of MMP-9 in TNF-induced proliferation and branching morphogenesis of mammary epithelial cells.   Endocrinology 141: 3764-3773.

J. Zhang, M.A. Warren, S.F. Shoemaker and M. M. Ip. (2007) NFkB1/p50 is not required for TNF-stimulated growth of primary mammary epithelial cells: implications for NFkB/p52 and RelB. Endocrinology 148: 268-278.

CLA project

P.A. Masso-Welch, D. Zangani, C. Ip, M.M. Vaughan, S. Shoemaker, R. A. Ramirez and M.M. Ip. (2002) Inhibition of angiogenesis by the chemopreventive agent conjugated linoleic acid.  Can. Res. 62: 4383-4389.

M.M. Ip, P.A. Masso-Welch and C. Ip.  (2003) Prevention of mammary cancer with conjugated linoleic acid:  role of the stroma and the epithelium.  J. Mammary Gland Biol. Neopl. 8: 101-116.

M.M. Ip, S.O. McGee, P.A. Masso-Welch, C. Ip, X. Meng, L. Ou, and S.F. Shoemaker (2007) The t10,c12 isomer of conjugated linoleic acid stimulates mammary tumorigenesis in transgenic mice over-expressing erbB2 in the mammary epithelium.   Carcinogenesis. 28: 1269-1276. 

X. Meng, S. Shoemaker, S.O. McGee and M. M. Ip (2008) t10,c12-Conjugated linoleic acid stimulates mammary tumor progression in her2/erbB2 mice through activation of both proliferative and survival pathways.   Carcinogenesis, in press.

L. Ou, Y. Wu, C. Ip, X. Meng, Y.-C. Hsu, and M. M. Ip (2008). Apoptosis induced by t10,c12-conjugated linoleic acid is mediated by an atypical endoplasmic reticulum stress response. J. Lipid Res. In press. doi:10.1194/jlr.M700465-JLR200.