例如:"lncRNA", "apoptosis", "WRKY"

Cyp24a1 Attenuation Limits Progression of -Induced Papillary Thyroid Cancer Cells and Sensitizes Them to BRAFV600E Inhibitor PLX4720.

Cancer Res.2017 Apr 15;77(8):2161-2172. Epub 2017 Feb 27
Minjing Zou 1 , Essa Y Baitei 1 , Huda A BinEssa 1 , Futwan A Al-Mohanna 2 , Ranjit S Parhar 2 , René St-Arnaud 3 , Shioko Kimura 4 , Catrin Pritchard 5 , Ali S Alzahrani 6 , Abdullah M Assiri 7 , Brian F Meyer 1 , Yufei Shi 8
Minjing Zou 1 , Essa Y Baitei 1 , Huda A BinEssa 1 , Futwan A Al-Mohanna 2 , Ranjit S Parhar 2 , René St-Arnaud 3 , Shioko Kimura 4 , Catrin Pritchard 5 , Ali S Alzahrani 6 , Abdullah M Assiri 7 , Brian F Meyer 1 , Yufei Shi 8
+ et al

[No authors listed]

Author information
  • 1 Department of Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
  • 2 Department of Cell Biology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
  • 3 Department of Surgery and Human Genetics, McGill University, Montreal, Quebec, Canada; and Research Centre, Shriners Hospitals for Children, Montreal, Quebec, Canada.
  • 4 Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
  • 5 Department of Biochemistry, University of Leicester, Lancaster Road, Leicester, UK.
  • 6 Department of Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
  • 7 Department of Comparative Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
  • 8 Department of Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. yufei@kfshrc.edu.sa.

摘要


CYP24A1, the primary inactivating enzyme for vitamin D, is often overexpressed in human cancers, potentially neutralizing the antitumor effects of calcitriol, the active form of vitamin D. However, it is unclear whether CYP24A1 expression serves as a functional contributor versus only a biomarker for tumor progression. In this study, we investigated the role of CYP24A1 on malignant progression of a murine model of -induced papillary thyroid cancer (PTC). Mice harboring wild-type Cyp24a1 (BVECyp24a1-wt) developed PTC at 5 weeks of age. Mice harboring a homozygous deletion of Cyp24a1 (BVECyp24a1-null) exhibited a 4-fold reduction in tumor growth. Notably, we found the tumorigenic potential of BVECyp24a1-null-derived tumor cells to be nearly abolished in immunocompromised nude mice. This phenotype was associated with downregulation of the MAPK, PI3K/Akt, and TGFβ signaling pathways and a loss of epithelial-mesenchymal transition (EMT) in BVECyp24a1-null cells, associated with downregulation of genes involved in EMT, tumor invasion, and metastasis. While calcitriol treatment did not decrease cell proliferation in BVECyp24a1-null cells, it strengthened antitumor responses to the BRAFV600E inhibitor PLX4720 in both BVECyp24a1-null and BVECyp24a1-wt cells. Our findings offer direct evidence that Cyp24a1 functions as an oncogene in PTC, where its overexpression activates multiple signaling cascades to promote malignant progression and resistance to PLX4720 treatment. Cancer Res; 77(8); 2161-72. ©2017 AACR.