Abstract
A new human tumor cell line, NCC‐c‐CX‐1 (CX‐1), was established from a uterine cervical cancer xenografted in nude mice. This cell line harbored approximately 50 to 100 copies of human papillomavirus (HPV) type 18 DNA per haploid genome, and contained about 16‐fold‐amplified c‐myc gene with rearrangement. These genomic alterations found in CX‐1 cells were also present in both primary tumor and xenografted tumor. Histopathologically, original and xenografted tumors were poorly differentiated cancer and were characterized by neuroendocrine features such as positive neuron‐specific enolase and chromogranin A by immunohistochemistry and abundant neurosecretory‐type granules in the cytoplasm by electron microscopy. However, the established cell line had lost the neuroendocrine features. This cervical cancer cell line may be a useful model for studying cervical carcinogenesis, especially the interaction between HPV and c‐myc oncogene.
Keywords: Cervical cancer cell line, c‐myc oncogene, Human papillomavirus, Neuroendocrine carcinoma
Full Text
The Full Text of this article is available as a PDF (627.3 KB).
REFERENCES
- 1. ) Zur Hausen , H.Herpes simplex virus in human genital cancer . Int. Rev. Exp. Pathol , 25 , 307 – 326 ( 1983. ). [PubMed] [Google Scholar]
- 2. ) Ocadiz , R. , Sauceda , R. , Cruz , M. , Graef , A. M. and Gariglio , P. ‘ High correlation between molecular alteration of the c‐myc oncogene and carcinoma of the uterine cervix ’. Cancer Res. , 47 , 4173 – 4177 ( 1987. ). [PubMed] [Google Scholar]
- 3. ) Riou , G. F. , Barrois , M. , Dutronquay , V. and Orth , G.Presence of papillomavirus DNA sequences, amplification of c‐myc and H‐ras oncogenes, and enhanced expression of c‐myc in carcinomas of the uterine cervix . In “ Papillo‐maviruses, Molecular and Clinical Aspects ,” ed. Howley P. M. and Broker T. R. , pp. 47 – 56 ( 1985. ). Alan R Liss, Inc. , New York . [Google Scholar]
- 4. ) Dust , M. , Croce , C. M. , Gissmann , L. , Schwarz , E. and Huebner , K.Papillomavirus sequences integrate near cellular oncogenes in some cervical carcinomas . Proc. Natl. Acad. Sci. USA , 84 , 1070 – 1074 ( 1987. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5. ) Choo , K. B. , Chong , K. Y. , Chou , H. F. , Liew , L. N. and Liou , C. C.Analysis of structure and expression of the c‐myc oncogene in cervical tumor and in cervical tumor‐derived cell lines . Biochem. Biophys. Res. Comtnun. , 158 , 334 – 340 ( 1989. ). [DOI] [PubMed] [Google Scholar]
- 6. ) Yee , C. , Krishnan‐Hewlett , I. , Baker , C. C. , Schlegel , R. and Howley , P. M.Presence and expression of human papillomavirus sequences in human cervical carcinoma cell lines . Am. J. Pathol , 119 , 361 – 366 ( 1985. ). [PMC free article] [PubMed] [Google Scholar]
- 7. ) Tsunokawa , Y. , Takebe , N. , Nozawa , S. , Kasamatsu , T. , Gissmann , L. , zur Hausen , H. , Terada , M. and Sugimura , T.Presence of human papillomavirus type‐16 and type‐18 DNA sequences and their expression in cervical cancers and cell lines from Japanese patients . Int. J. Cancer , 37 , 499 – 503 ( 1986. ). [DOI] [PubMed] [Google Scholar]
- 8. ) Schwartz , E. , Freese , U. K. , Gissmann , L. , Mayer , W. , Roggenbuck , B. , Stremlau , A. and zur Hausen , H.Structure and transcription of human papillomavirus sequences in cervical carcinoma cells . Nature , 314 , 111 – 115 ( 1985. ). [DOI] [PubMed] [Google Scholar]
- 9. ) Shirasawa , H. , Tomita , Y. , Sekiya , S. , Kamizawa , H. and Shimizu , B.Integration and transcription of human papillomavirus type 16 and 18 sequences in cell lines derived from cervical carcinomas . J. Gen. Virol , 68 , 583 – 591 ( 1987. ). [DOI] [PubMed] [Google Scholar]
- 10. ) Alitalo , K. , Schwab , M. , Lin , C. C. , Varmus , H. E. and Bishop , J. M.Homogeneously staining chromosomal regions contain amplified copies of an abundantly expressed cellular oncogene (c‐myc) in malignant neuro‐endocrine cells from a human colon carcinoma . Proc. Natl. Acad. Sci. USA , 80 , 1707 – 1711 ( 1983. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11. ) Westm , E. , Wong‐Staal , F. , Gehnann , E. P. , Favera , R. D. , Papas , T. S. , Lautenberger , J. A. , Eva , A. , Reddy , E. P. , Tronick , S. R. , Aaronson , S. A. and Gallo , R. C.Expression of cellular homologues of retroviral one genes in human hematopoietic cells . Proc Natl. Acad. Sci. USA , 79 , 2490 – 2494 ( 1982. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12. ) Little , C. D. , Nau , M. M. , Carney , D. N. , Gazder , A. F. and Minna , J. D.Amplification and expression of the c‐myc oncogenes in human lung cancer cell lines . Nature , 306 , 194 – 196 ( 1983. ). [DOI] [PubMed] [Google Scholar]
- 13. ) Riou , G. , Barrois , M. , Le , M. G. , George , M. , Doussal , V. L. and Haie , C.c‐myc proto‐oncogene expression and prognosis in early carcinoma of the uterine cervix . Lancet , ii , 761 – 763 ( 1987. ). [DOI] [PubMed] [Google Scholar]
- 14. ) Yokota , J. , Wada , M. , Yoshida , T. , Noguchi , M. , Terasaki , T. , Shimosato , Y. , Sugimura , T. and Terada , M.Heterogenity of lung cancer cells with respect to the amplification and rearrangement of myc family oncogenes . Oncogene , 2 , 607 – 611 ( 1988. ). [PubMed] [Google Scholar]
- 15. ) Yoshikawa , H. , Matsukura , T. , Yamamoto , E. , Kawana , T. , Mizuno , M. and Yoshiike , K.Occurrence of human papillomavirus types 16 and 18 DNA in cervical carcinomas from Japan: age of patients and histological type of carcinomas . Jpn. J. Cancer Res. , 76 , 667 – 671 ( 1985. ). [PubMed] [Google Scholar]
- 16. ) Wilczynski , S. P. , Bergen , S. , Walker , J. , Liao , S‐Y. and Pearlman , L.Human papillomaviruses and cervical cancer. Analysis of histopathologic features associated with different viral types . Hum. Pathol , 19 , 697 – 704 ( 1988. ). [DOI] [PubMed] [Google Scholar]
- 17. ) Ichimura , H. , Yamasaki , M. , Yamane , T. , Shimizu , H. , Katsumoto , T. , Kurimura , O. and Kurimura , T.Heterotransplantation of argyrophil small cell carcinoma of the uterine cervix integrating HPV16 DNA into nude mice . Jpn. J. Cancer Res. , 79 , 1255 – 1258 ( 1988. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18. ) Stoler , M. H. , Mills , S. E. , Gersel , D. J. and Walker , A. N.Small‐cell neuroendocrine carcinoma of the cervix. A human papillomavirus type 18‐associated cancer . Am. J. Surg. Pathol , 15 , 28 – 32 ( 1991. ). [DOI] [PubMed] [Google Scholar]
- 19. ) Gazdar , A. , Carney , D. , Baylm , S. and Guccion , J.Small cell carcinoma of the lung: altered morphological, biological and biochemical characteristics in long term cultures and heterotransplanted tumors . Proc. Am. Assoc, Cancer Res. , 21 , 51 ( 1980. ). [Google Scholar]
