title: Metastatic phenotype is regulated by estrogen in thyroid cells.
abstract: BACKGROUND
  Over 200 million people worldwide are affected by thyroid proliferative diseases, including cancer, adenoma, and goiter, annually. The incidences of thyroid malignancies are three to four times higher in women, suggesting the possible involvement of estrogen. Based on this observed sex bias, we hypothesize that estrogen modulates the growth and metastatic propensity of thyroid cancer cells.
  
  
  METHODS
  In this study, two thyroid cell lines (Nthy-ori 3-1 and BCPAP) were evaluated for the presence of estrogen receptor (ER) by Western blot analysis and estrogen responsiveness by using a cell proliferation assay. In addition, the effect of estradiol (E(2)) on modulation of metastatic phenotype was determined by using in vitro adhesion, migration, and invasion assays.
  
  
  RESULTS
  Thyroid cells expressed a functionally active ER-alpha and ER-beta as evidenced by 50-150% enhancement of proliferation in the presence of E(2). E(2) also enhanced adhesion, migration, and invasion of thyroid cells in an in vitro experimental model system that, based on our results, is modulated by beta-catenin.
  
  
  CONCLUSIONS
  Our data provide evidence that the higher incidence of thyroid cancer in women is potentially attributed to the presence of a functional ER that participates in cellular processes contributing to enhanced mitogenic, migratory, and invasive properties of thyroid cells. These findings will enable and foster the possible development of antiestrogenic therapy targeting invasion and migration, thus affecting metastatic propensity.
authors.affiliation: Department of Microbiology and Immunology, New York Medical College, Valhalla, New York 10595, USA.
authors.forename: Shilpi
authors.initials: S
authors.lastname: Rajoria
authors.forename: Robert
authors.initials: R
authors.lastname: Suriano
authors.forename: Arulkumaran
authors.initials: A
authors.lastname: Shanmugam
authors.forename: Yushan Lisa
authors.initials: YL
authors.lastname: Wilson
authors.forename: Stimson P
authors.initials: SP
authors.lastname: Schantz
authors.forename: Jan
authors.initials: J
authors.lastname: Geliebter
authors.forename: Raj K
authors.initials: RK
authors.lastname: Tiwari
mesh_terms: D002291:Carcinoma, Papillary / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000378:metabolism*; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000517:prevention & control; D010641:Phenotype; D021381:Protein Transport / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000378:metabolism* / Q000473:pathology*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D018841:HSP90 Heat-Shock Proteins; D051176:beta Catenin; D004958:Estradiol; D051057:Proto-Oncogene Proteins c-akt