Expression of the active Notch1 decreases MTC tumor growth in vivo. J Surg Res 2011 Nov;171(1):23-7
Date
05/17/2011Pubmed ID
21571316Pubmed Central ID
PMC3157562DOI
10.1016/j.jss.2011.03.035Scopus ID
2-s2.0-80052738552 (requires institutional sign-in at Scopus site) 21 CitationsAbstract
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.
MATERIALS AND 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.
CONCLUSION: Based on these data, activation of Notch signaling pathway could be a therapeutic strategy to treat patients with MTC.
Author List
Jaskula-Sztul R, Pisarnturakit P, Landowski M, Chen H, Kunnimalaiyaan MMESH terms used to index this publication - Major topics in bold
Achaete-Scute Complex Genome RegionAnimals
Anti-Bacterial Agents
Carcinoma, Medullary
Carcinoma, Neuroendocrine
Chromogranin A
Doxycycline
Gene Expression Regulation, Neoplastic
Male
Mice
Mice, Nude
Neoplasm Transplantation
Receptor, Notch1
Signal Transduction
Thyroid Neoplasms
Transplantation, Heterologous
