Dr. Margot Ip Margot Ip, PhD

Margot Ip


About Me


Dr. Margot Ip joined the staff of Roswell Park Comprehensive Cancer Center (Roswell Park) 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, Roswell Park (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.



Roswell Park Comprehensive Cancer Center
  • Department of Pharmacology and Therapeutics
Roswell Park Graduate Division, University at Buffalo
  • Professor Molecular Pharmacology and Cancer Therapeutics Program


Research 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.

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.


Gross KW, Gomez RA, Sigmund CD. Twists and turns in the search for the elusive renin processing enzyme: focus on "Cathepsin B is not the processing enzyme for mouse prorenin" . American journal of physiology. Regulatory, integrative and comparative physiology 2010; 298(5):R1209-R1211

Hsu Y-C, Meng X, Ou L, Ip MM. Activation of the AMP-activated protein kinase-p38 MAP kinase pathway mediates apoptosis induced by conjugated linoleic acid in p53-mutant mouse mammary tumor cells. Cellular signalling 2010;22(4):590-599

Liu W, Ip MM, Podgorsak MB, Das GM. Disruption of estrogen receptor alpha-p53 interaction in breast tumors: a novel mechanism underlying the anti-tumor effect of radiation therapy. Breast cancer research and treatment 2009;115(1):43-50

Warren MA, Shoemaker SF, Shealy DJ, Bshar W, Ip MM. Tumor necrosis factor deficiency inhibits mammary tumorigenesis and a tumor necrosis factor neutralizing antibody decreases mammary tumor growth in neu/erbB2 transgenic mice. Molecular cancer therapeutics 2009; 8(9):2655-2663

Meng X, Shoemaker SF, McGee SO, Ip MM. t10,c12-Conjugated linoleic acid stimulates mammary tumor progression in Her2/ErbB2 mice through activation of both proliferative and survival pathways. Carcinogenesis 2008; 29(5):1013-1021

Ou L, Wu Y, Ip C, Meng X, Hsu YC, Ip MM. Apoptosis induced by t10,c12-conjugated linoleic acid is mediated by an atypical endoplasmic reticulum stress response. Journal of lipid research 2008; 49(5):985-994

Ip MM, McGee SO, Masso-Welch PA, Ip C, Meng X, Ou L, Shoemaker SF. The t10,c12 isomer of conjugated linoleic acid stimulates mammary tumorigenesis in transgenic mice over-expressing erbB2 in the mammary epithelium.Carcinogenesis 2007; 28(6):1269-1276

Ou L, Ip C, Lisafeld B, Ip MM. Conjugated linoleic acid induces apoptosis of murine mammary tumor cells via Bcl-2 loss. Biochemical and biophysical research communications 2007; 356(4):1044-1049

Russell JS, McGee SO, Ip MM, Kuhlmann D, Masso-Welch PA. Conjugated linoleic acid induces mast cell recruitment during mouse mammary gland stromal remodeling. Journal of nutrition 2007; 137(5):1200-1207

Zhang J, Warren MA, Shoemaker SF, Ip MM. NFkappaB1/p50 is not required for tumor necrosis factor-stimulated growth of primary mammary epithelial cells: implications for NFkappaB2/p52 and RelB. Endocrinology 2007;148(1):268-278

Hsu Y-C, Ip MM. Conjugated linoleic acid-induced apoptosis in mouse mammary tumor cells is mediated by both G protein coupled receptor-dependent activation of the AMP-activated protein kinase pathway and by oxidative stress. Cellular signalling 2011; 23(12):2013-2020

Hsu Y-C, Ou L, Meng X, Ip MM. The PKA pathway plays a role in mediating trans-10, cis-12 conjugated linoleic acid-induced apoptosis in mouse mammary tumor cells. Proceedings of the American Association for Cancer Research Annual Meeting 2008; 49:296

Meng X, Ip MM. Trans-10, cis-12 conjugated linoleic acid stimulates mammary tumorigenesis in erbB2 transgenic mice. Proceedings of the American Association for Cancer Research Annual Meeting 2007; 48:805

Ou L, Wu Y, Ip C, Ip MM. Apoptosis induced by trans-10,cis-12 conjugated linoleic acid in mammary tumor cells is mediated through endoplasmic reticulum stress. Proceedings of the American Association for Cancer Research Annual Meeting 2007; 48:805