Ying C Henderson1, Soon-Hyun Ahn, Junsun Ryu, Yunyun Chen, Michelle D Williams, Adel K El-Naggar, Mihai Gagea, Rebecca E Schweppe, Bryan R Haugen, Stephen Y Lai, Gary L Clayman. 1. Departments of Head and Neck Surgery (Y.C.H., Y.C., S.Y.L., G.L.C.), Pathology (M.D.W., A.K.E-N.), Veterinary Medicine and Surgery (M.G.), Molecular and Cellular Oncology (S.Y.L.), and Cancer Biology (G.L.C.), The University of Texas MD Anderson Cancer Center, Houston, Texas 77030; Department of Otolaryngology-Head and Neck Surgery (S.H.A), College of Medicine, Seoul National University Bundang Hospital, Kyunggi-do, 463-707 Korea; Center for Thyroid Cancer (J.R), National Cancer Center, Goyang-si, Gyeonggi-do, 410-769 Korea; Department of Endocrinology (R.E.S., B.R.H.), University of Colorado at Denver Anschutz Medical Campus, Aurora, Colorado 80045.
Abstract
CONTEXT: Cell lines are a widely used tool in cancer research. However, despite the relatively high incidence of papillary thyroid carcinoma (PTC), there are only four PTC cell lines available for international research audience. OBJECTIVE: The objective of this study was to establish and characterize new PTC cell lines that represent primary tumor biology. Surgical specimens were obtained to generate PTC cell lines. Short tandem repeat profiling was used to confirm the uniqueness of the cell lines against databases of known cell lines and mutations were assessed using Sequenom. The expression of thyroid-specific genes was examined using real-time PCR. Tumorigenicity was determined using an orthotopic thyroid xenograft tumor mouse model. RESULTS: Six PTC cell lines (five conventional PTCs and one follicular variant of PTC) were generated and found to be unique when compared by short tandem repeat profiling against databases of all existing cell lines. The five conventional PTC cell lines carry the BRAF V600E mutation and the follicular variant of PTC cell line had an NRAS mutation. Five of the six cell lines had a mutation in the promoter of the human telomerase reverse transcriptase gene. None of the cell lines have RET/PTC rearrangements. Three cell lines were tumorigenic in the orthotopic thyroid xenograft tumor mouse model. CONCLUSIONS: These five characterized conventional PTC cell lines and the unique follicular variant of PTC cell line should be valuable reagents for thyroid cancer research. The three tumorigenic cell lines can be used for in vivo testing of targeted therapeutic and novel agents.
CONTEXT: Cell lines are a widely used tool in cancer research. However, despite the relatively high incidence of papillary thyroid carcinoma (PTC), there are only four PTC cell lines available for international research audience. OBJECTIVE: The objective of this study was to establish and characterize new PTC cell lines that represent primary tumor biology. Surgical specimens were obtained to generate PTC cell lines. Short tandem repeat profiling was used to confirm the uniqueness of the cell lines against databases of known cell lines and mutations were assessed using Sequenom. The expression of thyroid-specific genes was examined using real-time PCR. Tumorigenicity was determined using an orthotopic thyroid xenograft tumormouse model. RESULTS: Six PTC cell lines (five conventional PTCs and one follicular variant of PTC) were generated and found to be unique when compared by short tandem repeat profiling against databases of all existing cell lines. The five conventional PTC cell lines carry the BRAFV600E mutation and the follicular variant of PTC cell line had an NRAS mutation. Five of the six cell lines had a mutation in the promoter of the human telomerase reverse transcriptase gene. None of the cell lines have RET/PTC rearrangements. Three cell lines were tumorigenic in the orthotopic thyroid xenograft tumormouse model. CONCLUSIONS: These five characterized conventional PTC cell lines and the unique follicular variant of PTC cell line should be valuable reagents for thyroid cancer research. The three tumorigenic cell lines can be used for in vivo testing of targeted therapeutic and novel agents.
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