title: Expression of the active Notch1 decreases MTC tumor growth in vivo.
abstract: BACKGROUND
  Human medullary thyroid cancer (MTC) is a neuroendocrine (NE) tumor, derived from thyroid C-cells. Besides surgery, there are no curative therapies for MTC. This emphasizes the need for the development of new therapies. In MTC, Notch1 signaling pathway is absent and Notch1 activation in MTC-TT cells has been shown to reduce growth and NE markers in vitro. While the in vitro studies will provide insight into the potential mechanisms by which Notch inhibits growth, only by in vivo model one can recreate the conditions found in patients with MTC and assess effects on metastatic potential and microscopic disease.
  
  
  METHODS
  Doxycycline inducible TT-NOTCH1 cells were utilized in a murine subcutaneous xenograft model to study tumor development and growth. Doxycycline was used to induce the expression of Notch1 in these tumors.
  
  
  RESULTS
  Measurements of tumor volume showed that doxycycline treated mice had slower tumor growth than control mice. Western blot analysis of tumor lysates demonstrated activation of Notch1 protein only in doxycycline treated mice suggesting that active Notch1 slowed tumor growth. Furthermore, this activation led to a significant reduction in the levels of achaete-scute complex-like1 and chromogranin A important NE markers.
  
  
  CONCLUSIONS
  Based on these data, activation of Notch signaling pathway could be a therapeutic strategy to treat patients with MTC.
authors.affiliation: Department of Surgery Endocrine Surgery Research Laboratories, UW Carbone Cancer Center, University of Wisconsin, Madison, Wisconsin 53705, USA.
authors.forename: Renata
authors.initials: R
authors.lastname: Jaskula-Sztul
authors.forename: Pongthep
authors.initials: P
authors.lastname: Pisarnturakit
authors.forename: Michael
authors.initials: M
authors.lastname: Landowski
authors.forename: Herbert
authors.initials: H
authors.lastname: Chen
authors.forename: Muthusamy
authors.initials: M
authors.lastname: Kunnimalaiyaan
mesh_terms: D058145:Achaete-Scute Complex Genome Region / Q000235:genetics; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D018276:Carcinoma, Medullary / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D018278:Carcinoma, Neuroendocrine / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D053379:Chromogranin A / Q000235:genetics; D004318:Doxycycline / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D051881:Receptor, Notch1 / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014183:Transplantation, Heterologous
chemical_list: D000900:Anti-Bacterial Agents; D053379:Chromogranin A; C497762:Notch1 protein, mouse; D051881:Receptor, Notch1; D004318:Doxycycline