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Early cellular abnormalities induced by RET/PTC1 oncogene in thyroid-targeted transgenic mice

Oncogene volume 18, pages 3659–3665 (1999)Cite this article

Abstract

The RET/PTC1 oncogene, a rearranged form of the RET proto-oncogene, has been reported to be associated with human papillary thyroid carcinomas. We have shown that targeted expression of RET/PTC1 in the thyroid gland leads to the development of thyroid carcinomas in transgenic mice with histologic and cytologic similarities to human papillary thyroid carcinoma. To further investigate how RET/PTC1 expression contributes to the pathogenesis of papillary thyroid tumor, the time of tumor onset and the early phenotypic consequences of RET/PTC1 expression in thyrocytes were determined. All high copy transgenic mice developed bilateral thyroid tumors as early as 4 days of age. At embryological days 16 – 18, increased proliferation rate, distorted thyroid follicle formation and reduced radioiodide concentrating activity were identified in transgenic embryos. The reduced radioiodide concentrating activity was attributed to decreased expression of the sodium-iodide symporter. Our study showed that RET/PTC1 not only increased proliferation of thyrocytes, it also altered morphogenesis and differentiation. These findings provide a model for the role of RET/PTC1 in the formation of abnormal follicles with reduced iodide uptake ability observed in human papillary thyroid carcinoma.

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References

  • Bachrach LK, Eggo MC, Mak WW and Burrow GN. . 1985 Endocrinology 116: 1603–1609.

  • Bond JA, Wyllie FS, Rowson J, Radulescu A and Wynford-Thomas D. . 1994 Oncogene 9: 281–290.

  • Bongarzone I, Fugazzola L, Vigneri P, Mariani L, Mondellini P, Pacini F, Basolo F, Pinchera A, Pilotti S and Pierotti MA. . 1996 J. Clin. Endocrinol. Metab. 81: 2006–2009.

  • Buj-Bello A, Adu J, Pinon LG, Horton A, Thompson J, Rosenthal A, Chinchetru M, Buchman VL and Davies AM. . 1997 Nature 387: 721–724.

  • Dai G, Levy O and Carrasco N. . 1996 Nature 379: 458–460.

  • Di Renzo MF, Olivero M, Ferro S, Prat M, Bongarzone I, Pilotti S, Belfiore A, Costantino A, Bigneri R and Pierotti MA. . 1992 Oncogene 7: 2549–2553.

  • Grieco M, Santoro M, Berlingieri MT, Melillo RM, Donghi R, Bongarzone I, Pierotti MA, Della Porta G, Fusco A and Vecchio G. . 1990 Cell 60: 557–563.

  • Jhiang SM and Mazzaferri EL. . 1994 J. Lab. Clin. Med. 123: 331–337.

  • Jhiang SM, Sagartz JE, Tong Q, Parker-Thornburg J, Capen CC, Cho J-Y, Xing S and Ledent C. . 1996 Endocrinology 137: 375–378.

  • Jokinen MP and Botts S. . 1994 In: Pathology of tumors in laboratory animals: Vol. 2–tumors of the mouse, Vol. 2. Turusov, V. and Mohr, U. (eds). Iarc Scientific Publications: Lyon, France pp. 565–594.

    Google Scholar 

  • Klein RD, Sherman D, Ho WH, Stone D, Bennett GL, Moffat B, Vandlen R, Simmons L, Gu Q, Hongo JA, Devaux B, Poulsen K, Armanini M, Nozaki C, Asai N, Goddard A, Phillips H, Henderson CE, Takahashi M and Rosenthal A. . 1997 Nature 387: 717–721.

  • Klugbauer S, Lengfelder E, Demidchik EP and Rabes HM. . 1995 Oncogene 11: 2459–2467.

  • Lindsay RM and Yancopoulos GD. . 1996 Neuron 17: 571–574.

  • Santoro M, Carlomagno F, Hay ID, Herrmann MA, Grieco M, Melillo R, Pierotti MA, Bongarzone I, Della Porta G, Berger N, Peix JL, Paulin C, Fabien N, Vecchio G, Jenkins RB and Fusco A. . 1992 J. Clin. Invest. 89: 1517–1522.

  • Santoro M, Grieco M, Melillo RM, Fusco A and Vecchio G. . 1995 Eur. J. Endocrinol. 133: 513–522.

  • Smanik PA, Liu Q, Furminger TL, Ryu K, Xing S, Mazzaferri EL and Jhiang SM. . 1996 Biochem. Biophys. Res. Commun. 226: 339–345.

  • Smanik PA, Ryu K-Y, Theil KS, Mazzaferri EL and Jhiang SM. . 1997 Endocrinology 138: 3555–3558.

  • Tong Q, Xing S and Jhiang SM. . 1997 J. Biol. Chem. 272: 9043–9047.

  • Vega QC, Worby CA, Lechner MS, Dixon JE and Dressler GR. . 1996 Proc. Natl. Acad. Sci. USA 93: 10657–10661.

  • Yap AS, Stevenson BR, Cooper V and Manley SW. . 1997 Endocrinology 138: 2315–2324.

  • Zannini M, Avantaggiato V, Biffali E, Arnone MI, Sato K, Pischetola M, Taylor BA, Philips SJ, Simeone A and Di Lauro R. . 1997 EMBO J. 16: 3185–3197.

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Acknowledgements

We thank W Russo and L Eastman for animal care, Dr G Bijur for helping in computer image analysis, Dr K Mori and Dr WJ Devito at the University of Massachusetts Medical Center, (Worcester, MA, USA), for assistance with in situ hybridization protocol, Dr PN Graves at the Mount Sinai School of Medicine, (New York, NY, USA), for providing anti-TSHR polyclonal antibody, Dr HQ Nguyen at Amgen Inc. (Thousand Oaks, CA, USA), for assistance with BrdU immunohistochemistry, and J Schwartz for assistance with figure illustrations. We also acknowledge the use of the WM Keck Genetics Research Facility of the Neurobiotechnology Center. This study was supported by a grant from NIH, NCI (CA 60074) to SM Jhiang.

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Authors and Affiliations

  1. Department of Physiology, The Ohio State University, Columbus, OH 43210, Ohio, USA

    Je-Yoel Cho, Ernest L Mazzaferri & Sissy M Jhiang

  2. Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210, Ohio, USA

    John E Sagartz & Charles C Capen

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  1. Je-Yoel Cho
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  4. Ernest L Mazzaferri
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Cho, JY., Sagartz, J., Capen, C. et al. Early cellular abnormalities induced by RET/PTC1 oncogene in thyroid-targeted transgenic mice. Oncogene 18, 3659–3665 (1999). https://doi.org/10.1038/sj.onc.1202709

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