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Metastasizing Neuroblastomas from Taste Buds in Rats Transgenic for the Simian Virus 40 Large T Antigen under Control of the Probasin Gene Promoter

First Department of Pathology, Nagoya City University Medical School, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan

Naomi Hokaiwado

First Department of Pathology, Nagoya City University Medical School, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan

Young-Man Cho

First Department of Pathology, Nagoya City University Medical School, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan

Yoshihisa Ikeda

First Department of Pathology, Nagoya City University Medical School, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan

Satoru Takahashi

First Department of Pathology, Nagoya City University Medical School, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan

Tomoyuki Shirai

First Department of Pathology, Nagoya City University Medical School, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan

During establishment of a prostate cancer model in rats transgenic for the Simian virus 40 large T antigen, under control of the probasin gene promoter, with protein expression specific to the prostate, tongue, and spinal cord, undifferentiated small round cell tumors were frequently observed. Extensive examination of tongues of the transgenic rats, despite a macroscopically normal appearance, revealed the tumors to have come from taste buds of the papilla circumvallata and papilla foliata. The lesions were positive for the SV40 T antigen, PGP9.5 (ubiquitin C-terminal hydrolase), and synaptophysin, neuron and neuroendocrine markers. Morphologically and immunohistochemically, the tumors were diagnosed as neuroblastomas, considering the neuroepithelial origin. Histologically identical tumor cells in the spinal cord and lung were observed only in the rats with deeply invading tongue tumors, suggesting that metastasis from the tongue tumors had occurred. Castration or supplementation with testosterone propionate did not alter tumor development, indicating the tumors to be androgen-independent . These results clearly show that taste buds can give rise to metastasizing neuroblastomas.

Key Words: Tongue • endocrine carcinoma • small cell carcinoma • androgen-independent • synaptophysin • PGP9.5

References

• Adams JM, Cory S. ( 1991). Transgenic models of tumor development. Science 254: 1161—1167.[Abstract/Free Full Text]
• Asamoto M., Ochiya T., Toriyama-Baba H., Ota T., Sekiya T., Terada M., Tsuda H. (2000). Transgenic rats carrying human c-Ha-ras proto-oncogene s are highly susceptibletoN-methyl-N-nitrosoure a mammary carcinogenesis. Carcinogenesis 21: 243—249.[Abstract/Free Full Text]
• Bosland MC (1999). Use of animal models in defining efficacy of chemoprevention agents against prostate cancer. Eur Urol 35: 459—463.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Brinster RL, Chen HY, Messing A., van Dyke T., Levine AJ, Palmiter RD (1984). Transgenic mice harboring SV40 T-antigen genes develop characteristic brain tumors. Cell 37: 367—379.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Cui L., Mori T., Takahashi S., Imaida K., Akagi K., Yada H., Yaono M., Shirai T. (1998). Slight promotion effects of intermittent administration of testosterone propionate and/or diethylstilbestrol on 3,2'-dimethyl-4 -aminobiphenyl-initiate drat prostate carcinogenesis. Cancer Lett 122: 195— 199.
• DeCaprio JA, Ludlow JW, Figge J., Shew JY, Huang CM, Lee WH, Marsilio E., Paucha E., Livingston DM (1988). SV40 large tumor antigen forms a specific complex with the product of the retinoblastoma susceptibility gene. Cell 54: 275—283.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Dodd JG, Sheppard PC, Matusik RJ (1983). Characterization and cloning of rat dorsal prostate mRNAs. Androgen regulation of two closely related abundant mRNAs. J Biol Chem 258: 10731—10737.[Abstract/Free Full Text]
• Ermisch B., Schwechheimer K. (1995). Protein gene product (PGP). 9.5 in diagnostic (neuro-) oncology. An immunomorphological study. Clin Neuropathol 14: 130—136.[Web of Science][Medline] [Order article via Infotrieve]
• Greenberg NM, DeMayo F., Finegold MJ, Medina D., Tilley WD, Aspinall JO, Cunha GR, Donjacour AA, Matusik RJ, Rosen JM (1995). Prostate cancer in a transgenic mouse. Proc Natl Acad Sci USA 92: 3439—3443.[Abstract/Free Full Text]
• Greenberg NM, DeMayo FJ, Sheppard PC, Barrios R., Lebovitz R., Finegold M., Angelopoulou R., Dodd JG, Duckworth ML, Rosen JM, Matusik RJ (1994). The rat probasin gene promoter directs hormonally and developmentally regulated expression of a heterologous gene specifically to the prostate in transgenic mice. Mol Endocrinol 8: 230— 239.
• Hully JR, Su Y., Lohse JK, Griep AE, Sattler CA, Haas MJ, Dragan Y., Peterson J., Neveu M., Pitot HC (1994). Transgenic hepatocarcinogenesi s in the rat. Am J Pathol 145: 386—397.[Abstract]
• Hull MT, Eble JN, Warfel KA (1984). Extrapulmonary oat-cell carcinoma of the tongue: An electron-microscopic study. J Oral Pathol 13: 489—496.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Kanazawa H., Yoshie S. (1996). The taste bud and its innervation in the rat as studied by immunohistochemistry for PGP 9.5. Arch Histol Cytol 59: 357—367.[Web of Science][Medline] [Order article via Infotrieve]
• Kawabe M., Shibata MA, Sano M., Takesada Y., Tamano S., Ito N., Shirai T. (1997). Decrease of prostaglandin E2 and 5-bromo-2'-deoxyuridine labeling but not prostate tumor development by indomethacin treatment of rats given 3,2'-dimethyl-4-aminobiphenyl and testosterone propionate. Jpn J Cancer Res 88: 350—355.[CrossRef][Web of Science]
• Lane DP, Crawford LV (1979). T antigen is bound to a host protein in SV40-transformed cells. Nature 278: 261—263.[CrossRef][Medline] [Order article via Infotrieve]
• Linzer DI, Levine AJ (1979). Characterization of a 54K dalton cellular SV40 tumor antigen present in SV40-transformed cells and uninfected embryonal carcinoma cells. Cell 17: 43—52.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• McCormick DL, Rao KV, Steele VE, Lubet RA, Kelloff GJ, Bosland MC (1999). Chemoprevention of rat prostate carcinogenesis by 9-cis-retinoic acid. Cancer Res 59: 521—524.[Abstract/Free Full Text]
• Mitchell RB, Stedeford J., Buchanan G. (1998). Oat cell carcinoma of the tongue from an unknown primary. Ear Nose Throat J 77: 221— 223.
• Miyata E., Kawabe M., Sano M., Takesada Y., Takahashi S., Shirai T. (1997). Effects of tamoxifen, an antiestrogen, on rat prostate carcinogenesis by 3,2'-dimethyl-4-aminobiphenyl and testosterone do not support an estrogen role in testosterone promotion. Prostate 31: 9—13.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Pallas DC, Shahrik LK, Martin BL, Jaspers S., Miller TB, Brautigan DL, Roberts TM (1990). Polyoma small and middle T antigens and SV40 small t antigen form stable complexes with protein phosphatas e 2A. Cell 60: 167— 176.
• Rennie PS, Bruchovsky N., Leco KJ, Sheppard PC, McQueen SA, Cheng H., Snoek R., Hamel A., Bock ME, MacDonald BS (1993). Characterization of two cis-acting DNA elements involved in the androgen regulation of the probasin gene. Mol Endocrinol 7: 23—36.[Abstract/Free Full Text]
• Sharma P., Schreiber-Agus N. (1999). Mouse models of prostate cancer. Oncogene 18: 5349—5355.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Shibata MA, Ward JM, Devor DE, Liu ML, Green JE (1996). Progression of prostatic intraepithelial neoplasia to invasive carcinoma in C3(1)/SV40 large T antigen transgenic mice: histopathological and molecular biological alterations. Cancer Res 56: 4894—4903.[Abstract/Free Full Text]
• Shirai T., Imaida K., Masui T., Iwasaki S., Mori T., Kato T., Ito N. (1994). Effects of testosterone, dihydrotestosterone and estrogen on 3,2'-dimethyl4-aminobiphenyl-induce drat prostate carcinogenesis. IntJ Cancer 57:224— 228.
• Shirai T., Takahashi S., Cui L., Futakuchi M., Kato K., Tamano S., Imaida K. (2000). Experimental prostate carcinogenesis—rodent models. Mutat Res 462: 219—226.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Tsukamoto S., Akaza H., Onozawa M., Shirai T., Ideyama Y. (1998). A fivealpha reductase inhibitor or an antiandrogen prevents the progression of microscopic prostate carcinoma to macroscopic carcinoma in rats. Cancer 82: 531—537.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Wiedenmann B., Kuhn C., Schwechheimer K., Waldherr R., Raue F., Brandeis WE, Kommerell B., Franke WW (1987). Synaptophysin identified in metastases of neuroendocrine tumors by immunocytochemistry and immunoblotting. Am J Clin Pathol 88: 560—569.[Web of Science][Medline] [Order article via Infotrieve]

Toxicologic Pathology, Vol. 29, No. 3, 363-368 (2001)
DOI: 10.1080/019262301316905327


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This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Asamoto, M. Articles by Shirai, T. Search for Related Content PubMed PubMed Citation Articles by Asamoto, M. Articles by Shirai, T. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Neuroblastoma Prostate Cancer Tongue Disorders Social Bookmarking                         What's this?