"Ligand Independent" endocrine disruption by pesticides

Summary

Principal Investigator: PATRICK S WONG
Abstract: Chlorinated pesticides such as beta-hexachlorocyclohexane (a-HCH) and heptachlor epoxide have been proposed as risks factor for breast, endometrial and ovarian cancers. Their mechanisms of action may be due to their ability to mimic the effects of estrogen and thus, produce such effects as cell proliferation and down regulation of estrogen receptors which are associated with phenotypical markers of carcinogenesis. These pesticides, however, do not have agonistic properties toward estrogen receptors and thus, must exert their activity through some other mechanisms including a "ligand-independent" activation (LIA) mechanism similar to "crosstalk" patterns seen between growth factor receptors and estrogen receptors. Therefore, the main goals of this project are to establish the existence "ligand independent" activation mechanism for various chlorinated pesticides in our cell systems (BG-1 ovarian cancer cells, and Ishikawa endometrial cells). Secondly, experiments will be designed to dissect this LIA pathway for pesticides by investigating the molecular mechanisms which may be involved. This will be accomplished through the comparisons of the ability of chlorinated pesticide and established growth factor and cellular messenger activators to achieve LIA in the presence of possible LIA inhibitors (antibodies, second messenger inhibitors etc).
Funding Period: 2003-07-01 - 2006-06-30
more information: NIH RePORT

Top Publications

  1. ncbi Serum free BG-1 cell proliferation assay: a sensitive method for determining organochlorine pesticide estrogen receptor activation at the nanomolar range
    Patrick S Y Wong
    Center for Health and the Environment, Department of Environmental Toxicology, The University of California, 129 Old Davis Road, Davis, CA 95616, USA
    Toxicol In Vitro 20:382-94. 2006
  2. ncbi Mechanistic investigation on the cause for reduced toxicity of TCDD in wa-1 homozygous TGFalpha mutant strain of mice as compared its matching wild-type counterpart, C57BL/6J mice
    Nobuo Kitamura
    Department of Environmental Toxicology and Center for Environmental Health Sciences, University of California Davis, One Shields Avenue, Davis, CA 95616, USA
    J Biochem Mol Toxicol 20:151-8. 2006
  3. pmc Promotion of breast cancer by beta-hexachlorocyclohexane in MCF10AT1 cells and MMTV-neu mice
    PATRICK S WONG
    Center for Health and the Environment John Muir Institute of the Environment, Department of Environmental Toxicology, University of California, Davis, CA 95616, USA
    BMC Cancer 7:130. 2007
  4. pmc Arylhydrocarbon receptor activation in NCI-H441 cells and C57BL/6 mice: possible mechanisms for lung dysfunction
    PATRICK S WONG
    Center for Health and the Environment, University of California at Davis, 1 Shields Avenue, Davis, CA 95616, USA
    Am J Respir Cell Mol Biol 42:210-7. 2010
  5. pmc Characterization of MCF mammary epithelial cells overexpressing the Arylhydrocarbon receptor (AhR)
    PATRICK S WONG
    Department of Environmental Toxicology and the Center for Environmental Health Sciences, University of California, One Shields Ave, Davis, CA 95616, USA
    BMC Cancer 9:234. 2009

Scientific Experts

Detail Information

Publications5

  1. ncbi Serum free BG-1 cell proliferation assay: a sensitive method for determining organochlorine pesticide estrogen receptor activation at the nanomolar range
    Patrick S Y Wong
    Center for Health and the Environment, Department of Environmental Toxicology, The University of California, 129 Old Davis Road, Davis, CA 95616, USA
    Toxicol In Vitro 20:382-94. 2006
    ....
  2. ncbi Mechanistic investigation on the cause for reduced toxicity of TCDD in wa-1 homozygous TGFalpha mutant strain of mice as compared its matching wild-type counterpart, C57BL/6J mice
    Nobuo Kitamura
    Department of Environmental Toxicology and Center for Environmental Health Sciences, University of California Davis, One Shields Avenue, Davis, CA 95616, USA
    J Biochem Mol Toxicol 20:151-8. 2006
    ..These results indicate that a possible mechanism why wa/wa mice are less responsive to TCDD is that two genes encoding for the growth factor signaling components, c-Src and ERK-2, are not readily affected by TCDD...
  3. pmc Promotion of breast cancer by beta-hexachlorocyclohexane in MCF10AT1 cells and MMTV-neu mice
    PATRICK S WONG
    Center for Health and the Environment John Muir Institute of the Environment, Department of Environmental Toxicology, University of California, Davis, CA 95616, USA
    BMC Cancer 7:130. 2007
    ..In addition, long term exposure (33 passages) to beta-HCH was shown to promote the selection of MCF-7 cells which exhibit a more metastatic phenotype...
  4. pmc Arylhydrocarbon receptor activation in NCI-H441 cells and C57BL/6 mice: possible mechanisms for lung dysfunction
    PATRICK S WONG
    Center for Health and the Environment, University of California at Davis, 1 Shields Avenue, Davis, CA 95616, USA
    Am J Respir Cell Mol Biol 42:210-7. 2010
    ....
  5. pmc Characterization of MCF mammary epithelial cells overexpressing the Arylhydrocarbon receptor (AhR)
    PATRICK S WONG
    Department of Environmental Toxicology and the Center for Environmental Health Sciences, University of California, One Shields Ave, Davis, CA 95616, USA
    BMC Cancer 9:234. 2009
    ..At the same time, the AhR serves as the mediator of the cell survival program in the absence of ER signaling...