N-3 fatty acid & binding protein MRG on mammary tumor

Summary

Principal Investigator: Y Eric Shi
Abstract: [unreadable] DESCRIPTION (provided by applicant): There is an increasing public interest in chemoprevention by natural agents such as n-3 polyunsaturated fatty acids (PUFAs) DHA and EPA and the pregnancy-induced differentiation against breast cancer incidence. The mechanisms underlying these preventive effects are currently unknown. Little is known about the regional and developmental expression of locally acting factors in the mammary epithelium that interact with n-3 PUFA and exert differentiating effect during pregnancy. Within this content, a novel mammary derived growth inhibitor and a fatty acid binding protein (FABP) has recently been identified, characterized, and named Mammary derived growth inhibitor Related Gene (MRG). As a new member in the family of FABP, MRG has the highest binding affinity to n-3 PUFA DHA. The preliminary data indicate: (1) MRG overexpression suppresses breast cancer cell growth in vitro and tumorigenesis in vivo. (2) MRG induces differentiation of mammary epithelium and its expression is associated with human mammary gland differentiation. (3) MRG synergistically interacts with DHA in growth inhibition. The present application is to test the hypotheses that (a) MRG is a mediator for intracellular accumulation of n-3 PUFAs in mammary epithelial cells and mediates tumor suppressing effect of n-3 PUFAs on mammary tumors. In this regard, one of mechanisms for pregnancy-induced prevention may be mediated in part by PUFA composition change in mammary gland which favors the ratio of n-3 PUFAs to n-6 PUFAs following pregnancy and lactation; (b) MRG is mediator of the differentiating effects of pregnancy on breast epithelium and overexpression of MRG in young nulliparous mice can induce differentiation and protect the development of mammary tumors. We propose a series of studies of both in vitro and in MMTV/MRG transgenic mice to evaluate the role of MRG on mammary differentiation and tumorigenesis and its interaction with n-3 PUFA on mammary tumorigenesis. These studies will help to identify MRG as mediator for differentiation for mammary gland and for interaction with n-3 PUPA on inhibition of mammary tumorigenesis.
Funding Period: 2002-08-01 - 2008-07-31
more information: NIH RePORT

Top Publications

  1. pmc Vitexins, nature-derived lignan compounds, induce apoptosis and suppress tumor growth
    YingJun Zhou
    Central South University, Changsha, Hunan Province, China
    Clin Cancer Res 15:5161-9. 2009
  2. ncbi Activation of Stat5 and induction of a pregnancy-like mammary gland differentiation by eicosapentaenoic and docosapentaenoic omega-3 fatty acids
    Yiliang E Liu
    Feinstein Institute for Medical Research, Department of Radiation Oncology, Long Island Jewish Medical Center, The Albert Einstein College of Medicine, New Hyde Park, NY 11040, USA
    FEBS J 274:3351-62. 2007
  3. ncbi In-vitro synergism of m-TOR inhibitors, statins, and classical chemotherapy: potential implications in acute leukemia
    Anthony Calabro
    Experimental Therapeutics Section, Don Monti Division of Oncology, Monter Cancer Center, Lake Success, NY 11042, USA
    Anticancer Drugs 19:705-12. 2008

Scientific Experts

  • Y Eric Shi
  • YingJun Zhou
  • Anthony Calabro
  • Y Eric Shi
  • Weiping Pu
  • Yiliang E Liu
  • Cui Shen
  • Yiding Chen
  • Yiliang Ellie Liu
  • YanLan Li
  • Louis Potters
  • MeiChen Zhou
  • Jianguo Cao
  • GuangYao Zeng
  • Julia Tai
  • Daniel R Budman
  • Steven L Allen
  • Jingdong Wang
  • Jing X Kang

Detail Information

Publications3

  1. pmc Vitexins, nature-derived lignan compounds, induce apoptosis and suppress tumor growth
    YingJun Zhou
    Central South University, Changsha, Hunan Province, China
    Clin Cancer Res 15:5161-9. 2009
    ..We isolated a series of lignan compounds, named as Vitexins, from the seed of Chinese herb Vitex Negundo...
  2. ncbi Activation of Stat5 and induction of a pregnancy-like mammary gland differentiation by eicosapentaenoic and docosapentaenoic omega-3 fatty acids
    Yiliang E Liu
    Feinstein Institute for Medical Research, Department of Radiation Oncology, Long Island Jewish Medical Center, The Albert Einstein College of Medicine, New Hyde Park, NY 11040, USA
    FEBS J 274:3351-62. 2007
    ..Thus, alternation of n-6/n-3 fatty acid compositional ratio in favor of n-3 PUFA, and particularly docosapentaenoic acid and eicosapentaenoic acid, is one of the underlying mechanisms of pregnancy-induced mammary differentiation...
  3. ncbi In-vitro synergism of m-TOR inhibitors, statins, and classical chemotherapy: potential implications in acute leukemia
    Anthony Calabro
    Experimental Therapeutics Section, Don Monti Division of Oncology, Monter Cancer Center, Lake Success, NY 11042, USA
    Anticancer Drugs 19:705-12. 2008
    ..These effects were independent of whether or not human plasma was used in the assay system. These studies suggest several novel combinations of agents that need to be evaluated in the management of leukemia...