Exposure to beef growth promoter in breast cancer

Summary

Principal Investigator: YOUNG LIN
Abstract: Zeranol (Z) is a nonsteroidal agent with estrogenic activity that is used as a growth promoter in the U.S. beef and veal industries. Thus, people are exposed to Z via dietary intake as a consequence of the direct and intentional introduction of the compound into food animals by veterinary professionals on behalf of beef industry farmers. Our contention is that the consumption of food products, particularly beef, derived from food animals treated with Z has a potential health impact on human consumers, particularly with respect hormone-sensitive organs. This concern arises from our own experimental data using in vitro models derived from human breast cells and tissues which demonstrates the presence of heat-stable biological and estrogenic activity in extracts of meat derived from Z-treated cattle. These experimental data provide a putative link between the long-term dietary exposure to low-levels of Z and potential risk of breast cancer. The proposed study is designed to assess the relationship between exposure to Z via beef consumption and breast cancer in human subjects. Normal subjects and breast cancer patients will be categorized according to level of beef consumption. Levels of Z in breast, serum and urine and expression levels of mechanism-based molecular biomarkers in breast tissues will be determined as indicators of exposure and risk for breast cancer. Measurement of Z levels in purchased beef products from across the U.S., and confirmation of biological activity (mitogenic activity; altered expression of mechanism-based molecular biomarkers) in human and beef samples is aimed to solidify the association among beef consumption, Z exposure and breast cancer risk. The Specific Aims of the study are: (1) To develop an ELISA designed for the routine measurement of Z in commercial meats and human tissues and fluids; (2) To investigate relationships among beef consumption, levels of Z in breast, serum and urine, and breast cancer in patients of The Ohio State University Hospital; (3) To measure Z levels in commercially available beef products purchased in supermarkets from 5 different regions across the U.S.; and (4) To utilize established in vitro model systems to confirm the presence of biological activity (mitogenic activity; altered expression of mechanism-based molecular biomarkers) in specimens from human subjects and commercial beef products in which Z levels were detected. The proposed study utilizes our diverse multi disciplinary expertise in reproductive endocrinology, clinical and surgical oncology, breast cancer, veterinary medicine and medicinal chemistry to explore our contention that beef consumption may pose a human health risk. The proposed study will link beef production practices, beef consumption and human breast cancer in an integrated and comprehensive approach that will clarify the potential role of Z exposure in breast cancer, identify potentially valuable mechanism-based molecular biomarkers that could lead to new tools for exposure assessment in breast cancer, provide a fertile basis for future research directions in this important area, and provide information that may be useful to federal regulatory agencies in making informed decisions regarding the status of current regulations and practices in the use of growth promoters in beef destined for human consumption.
Funding Period: 2001-09-30 - 2005-08-31
more information: NIH RePORT

Top Publications

  1. ncbi Function and regulatory mechanisms of the candidate tumor suppressor receptor protein tyrosine phosphatase gamma (PTPRG) in breast cancer cells
    Sherry T Shu
    Laboratory of Reproductive and Molecular Endocrinology, Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210 1093, USA
    Anticancer Res 30:1937-46. 2010
  2. ncbi Keratinocyte growth factor (KGF) regulates estrogen receptor-alpha (ER-alpha) expression and cell apoptosis via phosphatidylinositol 3-kinase (PI3K)/Akt pathway in human breast cancer cells
    Hsiang Lin Chang
    Laboratory of Reproductive and Molecular Endocrinology, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA
    Anticancer Res 29:3195-205. 2009
  3. ncbi (-)-Gossypol reduces invasiveness in metastatic prostate cancer cells
    Yi Wen Huang
    Laboratory of Reproductive and Molecular Endocrinology, College of Veterinary Medicine, The Ohio State University, Columbus, OH, U S A
    Anticancer Res 29:2179-88. 2009
  4. pmc Conjugated linoleic acid induces apoptosis through estrogen receptor alpha in human breast tissue
    Li Shu Wang
    Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA
    BMC Cancer 8:208. 2008
  5. ncbi Primary cultured human breast epithelial cells up-regulate protein disulfide isomerase in response to zeranol
    Michael Scott Updike
    Department of Animal Sciences, College of Food, Agricultural and Environmental Sciences, College of Medicine and Public Health, The Ohio State University, Columbus, OH 43210, USA
    Anticancer Res 27:407-10. 2007
  6. ncbi Modulation of multidrug resistance gene expression in human breast cancer cells by (-)-gossypol-enriched cottonseed oil
    Weiping Ye
    Laboratory of Reproductive and Molecular Endocrinology, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210 1092, USA
    Anticancer Res 27:107-16. 2007
  7. ncbi Effects of serum on (-)-gossypol-suppressed growth in human prostate cancer cells
    Yi Wen Huang
    Laboratory of Reproductive and Molecular Endocrinology, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA
    Anticancer Res 26:3613-20. 2006
  8. ncbi Effect of keratinocyte growth factor on cell viability in primary cultured human prostate cancer stromal cells
    Yi Wen Huang
    Laboratory of Reproductive and Molecular Endocrinology, Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, 1900 Coffey Road, Columbus, OH 43210, USA
    J Steroid Biochem Mol Biol 100:24-33. 2006
  9. ncbi Molecular mechanisms of (-)-gossypol-induced apoptosis in human prostate cancer cells
    Yi Wen Huang
    Laboratory of Reproductive and Molecular Endocrinology, College of Veterinary Medicine and The Ohio State University, Columbus, OH 43210, USA
    Anticancer Res 26:1925-33. 2006
  10. ncbi Keratinocyte growth factor (KGF) induces tamoxifen (Tam) resistance in human breast cancer MCF-7 cells
    Hsiang Lin Chang
    Laboratory of Reproductive and Molecular Endocrinology, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA
    Anticancer Res 26:1773-84. 2006

Scientific Experts

  • Li Shu Wang
  • Yi Wen Huang
  • Young C Lin
  • Hsiang Lin Chang
  • Weiping Ye
  • Yasuro Sugimoto
  • Suling Liu
  • Michael K Dowd
  • Peter J Wan
  • Sherry T Shu
  • Michael Scott Updike
  • Sherry Shu
  • Macdonald Wick
  • Michael S Updike
  • Pearlly Yan
  • William B Farrar
  • Joseph C Sawdy
  • Michael E Davis

Detail Information

Publications14

  1. ncbi Function and regulatory mechanisms of the candidate tumor suppressor receptor protein tyrosine phosphatase gamma (PTPRG) in breast cancer cells
    Sherry T Shu
    Laboratory of Reproductive and Molecular Endocrinology, Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210 1093, USA
    Anticancer Res 30:1937-46. 2010
    ..To understand the tumor suppression characteristics of PTPRG, we studied its tumor suppressive function in an athymic mouse model and evaluated factors that can potentially regulate its expression in breast cancer cells...
  2. ncbi Keratinocyte growth factor (KGF) regulates estrogen receptor-alpha (ER-alpha) expression and cell apoptosis via phosphatidylinositol 3-kinase (PI3K)/Akt pathway in human breast cancer cells
    Hsiang Lin Chang
    Laboratory of Reproductive and Molecular Endocrinology, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA
    Anticancer Res 29:3195-205. 2009
    ..Therefore, we hypothesized that a possible mechanism for developing Tam resistance could be the regulation of ER-alpha and Bcl-2 family proteins through modulation of Akt activity...
  3. ncbi (-)-Gossypol reduces invasiveness in metastatic prostate cancer cells
    Yi Wen Huang
    Laboratory of Reproductive and Molecular Endocrinology, College of Veterinary Medicine, The Ohio State University, Columbus, OH, U S A
    Anticancer Res 29:2179-88. 2009
    ..Gossypol, a polyphenolic compound present in cottonseeds, possesses anti-proliferative and proapoptotic effects in various cancer cells...
  4. pmc Conjugated linoleic acid induces apoptosis through estrogen receptor alpha in human breast tissue
    Li Shu Wang
    Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA
    BMC Cancer 8:208. 2008
    ..Our research interest is to examine the effects of CLA on the induction of apoptosis in human breast tissues...
  5. ncbi Primary cultured human breast epithelial cells up-regulate protein disulfide isomerase in response to zeranol
    Michael Scott Updike
    Department of Animal Sciences, College of Food, Agricultural and Environmental Sciences, College of Medicine and Public Health, The Ohio State University, Columbus, OH 43210, USA
    Anticancer Res 27:407-10. 2007
    ..Research targets on gene-nutrient interactions may give useful information for the development of a novel diet-based intervention for the at-risk population...
  6. ncbi Modulation of multidrug resistance gene expression in human breast cancer cells by (-)-gossypol-enriched cottonseed oil
    Weiping Ye
    Laboratory of Reproductive and Molecular Endocrinology, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210 1092, USA
    Anticancer Res 27:107-16. 2007
    ....
  7. ncbi Effects of serum on (-)-gossypol-suppressed growth in human prostate cancer cells
    Yi Wen Huang
    Laboratory of Reproductive and Molecular Endocrinology, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA
    Anticancer Res 26:3613-20. 2006
    ..Here, the effect of bovine serum albumin (BSA) and dextran-coated charcoal-treated fetal bovine serum (DCC-FBS)-containing medium on the ability of (-)-gossypol to inhibit the growth of human prostate cancer cells was studied...
  8. ncbi Effect of keratinocyte growth factor on cell viability in primary cultured human prostate cancer stromal cells
    Yi Wen Huang
    Laboratory of Reproductive and Molecular Endocrinology, Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, 1900 Coffey Road, Columbus, OH 43210, USA
    J Steroid Biochem Mol Biol 100:24-33. 2006
    ..In summary, KGF has an autocrine effect and serves as a survival factor in primary cultured human prostate cancer stromal cells...
  9. ncbi Molecular mechanisms of (-)-gossypol-induced apoptosis in human prostate cancer cells
    Yi Wen Huang
    Laboratory of Reproductive and Molecular Endocrinology, College of Veterinary Medicine and The Ohio State University, Columbus, OH 43210, USA
    Anticancer Res 26:1925-33. 2006
    ..The (-)-gossypol enantiomer is a more potent inhibitor of cancer cell growth. Here, the molecular mechanisms of apoptosis induced by (-)-gossypol were studied in human prostate cancer cells...
  10. ncbi Keratinocyte growth factor (KGF) induces tamoxifen (Tam) resistance in human breast cancer MCF-7 cells
    Hsiang Lin Chang
    Laboratory of Reproductive and Molecular Endocrinology, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA
    Anticancer Res 26:1773-84. 2006
    ..In the present study, ER-alpha, two estrogen-regulated genes, PR and PTPgamma, KGF and their relationship with endocrine resistance in human breast cancer cells were investigated...
  11. ncbi Conjugated linoleic acid (CLA) modulates prostaglandin E2 (PGE2) signaling in canine mammary cells
    Li Shu Wang
    Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA
    Anticancer Res 26:889-98. 2006
    ..Moreover, a PGE2 receptor subtype, EP2, is highly expressed in mammary tumors. Thus, various studies have implicated the important role of PGE2 and EP2 in COX-2-regulated tumor development...
  12. ncbi Conjugated linoleic acid (CLA) up-regulates the estrogen-regulated cancer suppressor gene, protein tyrosine phosphatase gamma (PTPgama), in human breast cells
    Li Shu Wang
    Laboratory of Reproductive and Molecular Endocrinology, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA
    Anticancer Res 26:27-34. 2006
    ..Our previous results indicated that estradiol-17beta (E2)-induced suppression of PTPgamma may play a role in mammary tumorigenesis...
  13. ncbi Effects of human breast stromal cells on conjugated linoleic acid (CLA) modulated vascular endothelial growth factor-A (VEGF-A) expression in MCF-7 cells
    Li Shu Wang
    Laboratory of Reproductive and Molecular Endocrinology, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA
    Anticancer Res 25:4061-8. 2005
    ..Our previous results indicated that CLA induced suppression of VEGF-A in MCF-7 cells, which may be one of CLA's anticancer mechanisms...
  14. ncbi Decreased MCF-7 breast cancer cell proliferation by serum from a selected line of beef cattle
    Michael S Updike
    Department of Animal Sciences, The Ohio State University, Columbus, OH 43210, USA
    Anticancer Res 25:871-4. 2005
    ..In conclusion, model systems employing agricultural animals may provide novel insight into mechanisms of cell proliferation...