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Expression of Wild-Type p53 Tumor Suppressor Gene and Its possible Involvement in the Apoptosis of Thyroid Tumors

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Abstract

A good prognosis is often achieved in patients who have undergone treatment for human papillary carcinoma of the thyroid. On the assumption that this may be partly attributable to an apoptotic tendency of this special type of tumor, we measured DNA fragmentation, cell death by enzymelinked immunosorbent assay (ELISA), and the expression of apoptosis-related genes. DNA fragmentation occurred more extensively in malignant tumor cells than in benign thyroid tumors or normal thyroid tissue, as examined by agarose gel electrophoresis and confirmed by the quantitative method using an ELISA kit. Although only expression of the tumor suppressor gene,p53, was increased in the tumor tissue, no expression of other genes, such asFas, TNF, c-myc, c-fos orbcl-2, was observed in the normal, benign, or malignant tumor tissues, indicating that the roles of these gene functions, if any, were minimal in these tissues. Sincep53 is closely related to cellular apoptosis and no point mutation was observed in the transcripts expressed by malignant cells, apoptosis and/or the production of an angiogenesis inhibitor induced by wild-typep53 molecules may be related to the favorable prognosis of patients treated for papillary carcinoma of the thyroid.

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References

  1. George SL (1986) Nodular goiter and benign and malignant neoplasms of the thyroid. In: Sabiston DC (ed) Textbook of surgery, vol 1. Saunders, Philadelphia, pp 595–610

    Google Scholar 

  2. Raff MC (1992) Social controls on cell survival and cell death. Nature 356:397–400

    Google Scholar 

  3. Williams GT (1991) Programmed cell death: apoptosis and oncogenesis. Cell 65:1097–1098

    Google Scholar 

  4. Marx J (1993) Cell death studies yield cancer clues. Science 259:760–761

    Google Scholar 

  5. Kerr JFR, Wyllie AH, Currie AR (1972) Apoptosis: A basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26:239–245

    Google Scholar 

  6. Kerr JFR, Winterford CM, Harmon BV (1994) Apoptosis. Cancer 73:2013–2026

    Google Scholar 

  7. Hollstein M, Sidransky D, Vogelstein B, Harris CC (1991) p53 mutations in human cancers. Science 252:49–53

    Google Scholar 

  8. Levine AJ, Momand J, Finlay CA (1991) The p53 tumour suppressor gene. Nature 351:453–456

    Google Scholar 

  9. Varda R, Miron P (1991) p53 and human malignancies. Adv Cancer Res 57:257–272

    Google Scholar 

  10. Oren M, Reich NC, Levine AJ (1982) Regulation of the p53 tumor antigen in teratocarcinoma cells and their differentiated progeny. Mol Cell Biol 2:443–449

    Google Scholar 

  11. Mercer WE, Avignolo C, Baserga R (1984) Role of the p53 protein in cell proliferation as studied by microinjection of monoclonal antibodies. Mol Cell Biol 4:276–281

    Google Scholar 

  12. Finlay CA, Hinds PW, Tan TH, Eliyahu D, Oren M, Levine AJ (1988) Activating mutations for transformation by p53 produce a gene product that forms an hsc70-p53 complex with an altered half life. Mol Cell Biol 8:531–539

    Google Scholar 

  13. Fritsche M, Haessler C, Brandner G (1993) Induction of nuclear accumulation of the tumor-suppressor protein p53 by DNAdamaging agents. Oncogene 8:307–318

    Google Scholar 

  14. Lane DP (1992) p53, guardian of the genome. Nature 358:15–16

    Google Scholar 

  15. Shaw P, Bovery R, Tardy S, Sahli R, Sordat B, Costa J (1992) Induction of apoptosis by wild-type p53 in a human colon tumorderived cell line. Proc Nat] Acad Sci USA 89:4495–4499

    Google Scholar 

  16. Fujiwara T, Grimm EA, Mukhopadhyay T, Zhang WW, OwenSchaub LB, Roth JA (1994) Induction of chemosensitivity in human lung cancer cells in vivo by adenovirus-mediated transfer of the wild-type p53 gene. Cancer Res 54:2287–2291

    Google Scholar 

  17. Lowe SW, Schmitt EM, Smith SW, Osborne BA, Jacks T (1993) p53 is required for radiation-induced apoptosis in mouse thymocytes. Nature 362:847–848

    Google Scholar 

  18. Barry MA, Behnke CA, Eastman A (1990) Activation of programmed cell death by cisplatin, other anticancer drugs, toxins and hyperthermia. Biochem Pharmacol 40:2353–2362

    Google Scholar 

  19. Chomczynski P, Sacchi N (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162:156–159

    Google Scholar 

  20. Wakatsuki T, Kimura K, Kimura F, Shinomiya N, Ohtsubo M, Ishizawa M, Yamamoto M (1995) A distinct mRNA encoding a soluble form of ICAM-1 molecule expressed in human tissues. Cell Adh Commun 3:283–292

    Google Scholar 

  21. Hsu SM, Rainel L, Fanger H (1981) A comparative study of the peroxidase-antiperoxidase method and an avidin-biotin complex method for studying peptide hormones with radioimmunoassay antibodies. Am J Clin Pathol 75:734–738

    Google Scholar 

  22. Hiraishi K, Suzuki K, Hakomori S, Adachi M (1993) Ley antigen expression is correlated with apoptosis (programmed cell death). Glycobiology 3:381–390

    Google Scholar 

  23. Oren M (1992) p53; the ultimate tumor suppressor gene? FASEB 16:169–176

    Google Scholar 

  24. Ginsberg D, Michael-Michalovitz D, Ginsberg D, Pren M (1991) Induction of growth arrest by a temperature-sensitive p53 mutant is correlated with increased nuclear localization and decreased stability of the protein. Mol Cell Biol 11:582–585

    Google Scholar 

  25. Nigro JM, Baker SJ, Preisinger AC, Jessup JM, Hostetter R, Cleary K, Biggner SH, Davidson N, Baylin S, Devilee P, Glover T, Collins FS, Weston A, Modali R, Harris CC, Vogelstein B (1989) Mutations in the p53 gene occur in diverse human tumour types. Nature 342:705–708

    Google Scholar 

  26. Harris CC, Hollstein M (1993) Clinical implications of the p53 tumor suppressor gene. N Engl J Med 329:1318–1327

    Google Scholar 

  27. Greenblatt MS, Bennet WP, Hollstein M, Harris CC (1994) Mutations in the p53 tumor suppressor gene; clue to cancer etiology and molecular pathogenesis. Cancer Res 54:4855–4878

    Google Scholar 

  28. Van Meri EG, Polverini PJ (1994) Release of an inhibitor of angiogenesis upon induction of wild type p53 expression in glioblastoma cell. Nature Genet 8:171–176

    Google Scholar 

  29. Bedi A, Pasricha PJ, Akhtas AJ, Barber JP, Bedi GC, Giardiella FM, Zehnbader BA, Hamilton SR, Jones RJ (1995) Inhibition of apoptosis during development of colorectal cancer. Cancer Res 55:1811–1816

    Google Scholar 

  30. Miyashita T, Krajewski S, Krajierska M, Wang HG, Lin HK, Liebermann DA, Hoffman B, Read JC (1994) Tumor suppressor p53 is a regulator of bcl-2 and bax gene expression in vitro and vivo. Oncogene 9:1799–1805

    Google Scholar 

  31. Miyashita T, Reed JC (1995) Tumor suppressor p53 is a direct transcriptional activator of the human bax gene. Cell 80:293–299

    Google Scholar 

  32. Fasin JA (1992) Genetic basis of endocrine disease 3: molecular defects in thyroid gland neoplasia. J Clin Endocrinol Metab 75:1398–1400

    Google Scholar 

  33. Fasin JA (1993) High prevalence of mutations of the p53 gene in poorly differentiated human thyroid carcinomas. J Clin Invest 91:179–184

    Google Scholar 

  34. Shimizu T (1993) Proliferative activity of human thyroid tumors evaluated by proliferating cell nuclear antigen/cyclin immunohistochemical studies. Cancer 71:2807–2812

    Google Scholar 

  35. Haugen DFR, Akslen LA, Varhaug JE, Lillehaug JR (1992) Expression of c-erbB2 protein in papillary thyroid carcinomas. Br J Cancer 65:832–837

    Google Scholar 

  36. Aasland R, Lillehaug JR, Male R, Josendal O, Varhaug JE, Kleppe K (1988) Expression of oncogenes in thyroid tumors: Coexpression of c-erbB2/neu and c-erbB. Br J Cancer 57:358–363

    Google Scholar 

  37. Hsu H, Xiong J, Goeddel DV (1995) The TNF receptor 1associated protein TRADD signals cell death and NF-kB activation. Cell 81:495–504

    Google Scholar 

  38. Nagata S, Golstein P (1995) The Fas death factor. Science 267:1449–1456

    Google Scholar 

  39. Cheng J, Zhou T, Liu C, Shanpiro JP, Brauer MJ, Kiefer MC, Barr PL, Mountz JD (1994) Protection from Fas-mediated apoptosis by a soluble form of the Fas molecule. Science 263:1759–1762

    Google Scholar 

  40. Hockenbery DM, Nunez G, Milliman C, Schreiber RD, Korsmeyer SJ (1990) Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death. Nature 348:334–336

    Google Scholar 

  41. Fanidi A, Harrington EA, Evan GI (1992) Cooperative interaction between c-myc and bcl-2 and proto-oncogenes. Nature 359:554–556

    Google Scholar 

  42. Frank A (1995) bcl-2 and p53 oncoprotein expression during colorectal tumorigenesis. Cancer Res 55:237–241

    Google Scholar 

  43. Pilotti S, Collini P, Rilke F, Cattoretti G, Bo RD, Pierotti MA (1994) Bcl-2 protein expression in carcinomas originating from the follicular epithelium of the thyroid gland. J Pathol 172:337–342

    Google Scholar 

  44. Tanimoto C, Hirakawa S, Kawasaki H, Hayakawa N, Ota Z (1995) Apoptosis in thyroid disease; A histochemical study. Endocrine J 42:193–201

    Google Scholar 

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Kikuchi, S., Hiraide, H., Tamakuma, S. et al. Expression of Wild-Type p53 Tumor Suppressor Gene and Its possible Involvement in the Apoptosis of Thyroid Tumors. Surg Today 27, 226–233 (1997). https://doi.org/10.1007/BF00941650

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