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Oxyphilic and non-oxyphilic thyroid carcinoma cell lines differ in expressing apoptosis-related genes

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Abstract

Oxyphilic tumors of the thyroid are characterized by mitochondrion-rich cells and extensive DNA fragmentation. In order to clarify if a different expression of apoptosis-related genes could be responsible for DNA fragmentation in oxyphilic cell tumors, two thyroid follicular carcinoma-derived cell lines, having oxyphilic (XTC.UC1) and non-oxyphilic (WRO) features, were compared applying a gene array technique. Under basal culture conditions, several pro-apoptotic genes [caspases 3 and 10, Fas and the tumor necrosis factor-related apoptosis-inducing ligand (trail) genes] were switched on in oxyphilic, but not in non-oxyphilic cells. No difference in the mitochondrial apoptosis-related genes (bax, bad, bcl family etc.) was observed. Using the ISEL technique, the extent of DNA fragmentation did not differ under basal conditions in the two cell lines. Conversely, following an oxidative pro-apoptotic stress (6-h methylene blue treatment and light exposure), XTC.UC1 cells showed an extensive DNA fragmentation (up to 70% of cells), dramatically exceeding that observed in WRO cells (up to 20% of cells). In contrast, the oxidative stimulus induced a remarkable apoptosis gene activation in non-oxyphilic WRO cells only. These results suggest that oxyphilic cells may have a unique silent activation of a pro-apoptotic phenotype, which could be responsible for DNA instability and lead to cell death as the consequence of an increased sensitivity to ischemic stresses, as frequently observed in vivo.

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References

  1. Rosai J, Carcangiu ML, DeLellis RA. Tumors of the thyroid gland. Atlas of Tumor Pathology (3rd series). Washington: Armed Forces Institute of Pathology. 1992.

    Google Scholar 

  2. Reenan RA, Kolodner RD. Characterization of insertion mutations in the Saccharomyces cerevisiae MSH1 and MSH2 genes: evidence for separate mitochondrial and nuclear functions. Genetics 1992, 132: 975–85.

    PubMed Central  PubMed  CAS  Google Scholar 

  3. Maximo V, Soares P, Lima J, Cameselle-Teijero J, Sobrinho-Simões M. Mitochondrial DNA somatic mutations (point mutations and large deletions) and mitochondrial DNA variants in human thyroid pathology. A study with emphasis on Hürthle cell tumors. Am J Pathol 2002, 160: 1857–65.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  4. Tallini G, Hsueh A, Liu S, Garcia-Rostan G, Speicher MR, Ward DC. Frequent chromosomal DNA unbalance in thyroid oncocytic (Hürthle cell) neoplasm detected by comparative genomic hybridization. Lab Invest 1999, 79: 547–55.

    PubMed  CAS  Google Scholar 

  5. Maximo V, Sobrinho-Simões M. Mitochondrial DNA ‘common’ deletion in Hürthle cell lesions of the thyroid. J Pathol 2000, 192: 561–2.

    Article  PubMed  CAS  Google Scholar 

  6. Tallini G, Ladanyi M, Rosai J, Jhanwar SC. Analysis of nuclear and mitochondrial DNA alterations in the thyroid and renal oncocytic tumors. Cytogenet Cell Genet 1994, 66: 253–9.

    Article  PubMed  CAS  Google Scholar 

  7. Ebner D, Rodel G, Pavenstaedt I, Haferkamp O. Functional and molecular analysis of mitochondria in thyroid oncocytoma. Virchows Arch 1991, 60: 139–44.

    Article  CAS  Google Scholar 

  8. Tremblay G, Pearse AGE. Histochemistry of oxidative enzyme systems in the human thyroid with special reference to Askanazy cells. J Pathol Bacteriol 1960, 80: 353–8.

    Article  PubMed  CAS  Google Scholar 

  9. Valenta LJ, Michel-Bechet M, Warshaw JB, Maloof F. Human thyroid tumors composed of mitochondrion-rich cells: electron microscopic and biochemical findings. J Clin Endocrinol Metab 1974, 39: 719–33.

    Article  PubMed  CAS  Google Scholar 

  10. Chang A, Harawi SJ. Oncocytes, oncocytosis, and oncocytic tumors. Pathol Annu 1992, 27: 263–304.

    PubMed  Google Scholar 

  11. Attardi G, Yoneda M, Chomyn A. Complementation and segregation behaviour of disease-causing mitochondrial DNA mutations in cellular model systems. Biochim Biophys Acta 1995, 1271: 241–8.

    Article  PubMed  Google Scholar 

  12. Ramp U, Pfitzer P, Gabbert HE. Fine needle aspiration (FNA)-induced necrosis of tumours of the thyroid. Cytopathology 1995, 6: 248–54.

    Article  PubMed  CAS  Google Scholar 

  13. Volante M, Papotti M, Gugliotta P, Migheli A, Bussolati G. Extensive DNA fragmentation in oxyphilic cell lesions of the thyroid. J Histochem Cytochem 2001, 49: 1003–11.

    Article  PubMed  CAS  Google Scholar 

  14. Deregibus MC, Cantaluppi V, Doublier S, et al. HIV-1-Tat protein activates phosphatidylinositol 3-kinase/Akt-dependent survival pathways in Kaposis’s sarcoma cells. J Biol Chem 2002, 277: 25195–202.

    Article  PubMed  CAS  Google Scholar 

  15. Zielche A, Tezelman S, Jossart GH, et al. Establishment of a highly differentiated thyroid cancer cell line of Hürthle cell origin. Thyroid 1998, 8: 475–83.

    Article  Google Scholar 

  16. Schatz G. Mitochondria: beyond oxidative phosphorylation. Biochim Biophys Acta 1995, 1271: 123–6.

    Article  PubMed  Google Scholar 

  17. Mihara K. Targeting and insertion of nuclear-encoded preproteins into mitochondrial outer membrane. Bioessays 2000, 22: 364–71.

    Article  PubMed  CAS  Google Scholar 

  18. Grossman LI, Shoubridge EA. Mitochondrial genetics and human disease. Bioessays 1996, 18: 983–91.

    Article  PubMed  CAS  Google Scholar 

  19. Corral-Debrinski M, Horton T, Lott MT, Shoffner JM, Beal MF, Wallace DC. Mitochondrial DNA deletions in human brain: regional variability and increase with advanced age. Nat Genet 1992, 2: 324–9.

    Article  PubMed  CAS  Google Scholar 

  20. Polyak K, Li Y, Zhu H, et al. Somatic mutations of the mitochondrial genome in human colorectal tumours. Nat Genet 1998, 20: 291–3.

    Article  PubMed  CAS  Google Scholar 

  21. Warburg O. On the origin of cancer cells. Science 1956, 123: 309–14.

    Article  PubMed  CAS  Google Scholar 

  22. Savagner F, Franc B, Guyetant S, Rodien P, Reynier P, Malthiery Y. Defective mitochondrial ATP synthesis in oxyphilic thyroid tumors. J Clin Endocrinol Metab 2001, 86: 4920–5.

    Article  PubMed  CAS  Google Scholar 

  23. Savagner F, Chevrollier A, Loiseau D, et al. Mitochondrial activity in XTC-UC1 cells derived from thyroid oncocytoma. Thyroid 2001, 11: 327–33.

    Article  PubMed  CAS  Google Scholar 

  24. Muller-Hocker J. Random cytochrome-c-oxidase deficiency of oxyphil cell nodules in the parathyroid gland. A mitochondrial cytopathy related to cell ageing? Pathol Res Pract 1992, 188: 701–6.

    Article  PubMed  CAS  Google Scholar 

  25. Mitsiades N, Poulaki V, Tseleni-Balafouta S, Koutras DA, Stamenkovic I. Thyroid carcinoma cells are resistant to FASmediated apoptosis but sensitive tumor necrosis factor-related apoptosis-inducing ligand. Cancer Res 2000, 60: 4122–9.

    PubMed  CAS  Google Scholar 

  26. Bodmer JL, Holler N, Reynard S, et al. TRAIL receptor-2 signals apoptosis through FADD and caspase-8. Nat Cell Biol 2000, 2: 241–3.

    Article  PubMed  CAS  Google Scholar 

  27. Sprick MR, Weigand MA, Reiser E, et al. FADD/MORT1 and caspase-8 are recruited to TRAIL receptors 1 and 2 and are essential for apoptosis mediated by TRAIL receptor 2. Immunity 2000, 12: 599–609.

    Article  PubMed  CAS  Google Scholar 

  28. Kischkel FC, Lawrence DA, Chuntharapai A, Schow P, Kim KJ, Ashkenazi A. Apo2L/TRAIL-dependent recruitment of endogenous FADD and caspase-8 to death receptors 4 and 5. Immunity 2000, 12: 611–20.

    Article  PubMed  CAS  Google Scholar 

  29. Yoshioka K, Nakamori S, Itoh K. Overexpression of small GTP-binding protein RhoA promotes invasion of tumor cells. Cancer Res 1999, 59: 2004–10.

    PubMed  CAS  Google Scholar 

  30. del Peso L, Hernandez-Alcoceba R, Embade N, et al. Rho proteins induce metastatic properties in vivo. Oncogene 1997, 15: 3047–57.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Biomedical Sciences and Oncology, University of Torino, Torino, Italy

    E. Allìa, P. Cassoni, T. Marrocco, M. Volante & Mauro Papotti MD

  2. Department of Clinical and Biological Sciences, University of Torino, Torino, Italy

    B. Bussolati

  3. Department of Surgery, University of California, San Francisco/Mount Zion Medical Center, San Francisco, CA, USA

    M. Wong & O. H. Clark

Authors
  1. E. Allìa
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  2. P. Cassoni
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  3. T. Marrocco
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  4. M. Volante
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  5. B. Bussolati
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  6. M. Wong
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  7. O. H. Clark
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  8. Mauro Papotti MD
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Correspondence to Mauro Papotti MD.

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Work supported by grants from the Italian Ministry of University and Research, Rome.

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Allìa, E., Cassoni, P., Marrocco, T. et al. Oxyphilic and non-oxyphilic thyroid carcinoma cell lines differ in expressing apoptosis-related genes. J Endocrinol Invest 26, 660–667 (2003). https://doi.org/10.1007/BF03347026

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  • DOI: https://doi.org/10.1007/BF03347026

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