Abstract
We examined the expression of ret proto‐oncogene (proto‐ret) in surgically resected human neuroblastomas. Slot blot RNA hybridization revealed that all 29 neuroblastomas examined expressed the proto‐ret, the relative intensity of the hybridization ranging from 1 to 48. No correlation was found between the level of expression of proto‐ret and the clinical stage. The level of expression was also not correlated with N‐myc amplification, the patient's age or the histological type of the tumor. Based on the previous finding that proto‐ret expression is very rarely detected in tumor cell lines other than those of neuroblastoma, proto‐ret expression was suggested to be a characteristic of neuroblastomas, and possibly to be involved in the genesis of neuroblastomas.
Keywords: Neuroblastoma, Expression of ret proto‐oncogene, Clinical stage, N‐myc amplification
Full Text
The Full Text of this article is available as a PDF (232.1 KB).
REFERENCES
- 1. ) Breslow , N. and McCann , B.Statistical estimation of prognosis for children with neuroblastoma . Cancer Res. , 31 , 2098 – 2103 ( 1971. ). [PubMed] [Google Scholar]
- 2. ) Schwab , M. , Ellison , J. , Busch , M. , Rosenau , W. , Varmus , H. E. and Bishop , J. M.Enhanced expression of the human gene N‐myc consequent to amplification of DNA may contribute to malignant progression of neuroblastoma . Proc. Natl. Acad. Sci. USA , 81 , 4940 – 4944 ( 1984. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3. ) Seeger , R. C. , Brodeur , G. M. , Sather , H. , Dalton , A. , Siegel , S. E. , Wong , K. Y. and Hammond , D.Association of multiple copies of the N‐myc oncogene with rapid progression of neuroblastomas . N. Engl. J. Med. , 313 , 1111 – 1116 ( 1985. ). [DOI] [PubMed] [Google Scholar]
- 4. ) Gilbert , F. , Feder , M. , Balaban , G. , Brangman , D. , Lurie , D. K. , Podolsky , R. , Rinaldt , V. , Vinikoor , N. and Weisband , J.Human neuroblastomas and abnormalities of chromosome 1 and 17 . Cancer Res. , 44 , 5444 – 5449 ( 1984. ). [PubMed] [Google Scholar]
- 5. ) Suzuki , T. , Yokota , J. , Mugishima , H. , Okabe , I. , Ookuni , M. , Sugimura , T. and Terada , M.Frequent loss of heterozygosity on chromosome 14q in neuroblastoma . Cancer Res. , 49 , 1095 – 1098 ( 1989. ). [PubMed] [Google Scholar]
- 6. ) Fong , C‐T. , Dracopoli , N. C. , White , P. S. , Merrill , P. T. , Griffith , R. C. , Housman , D. E. and Brodeur , G. M.Loss of heterozygosity for the short arm of chromosome 1 in human neuroblastoma: correlation with N‐myc amplification . Proc. Natl. Acad. Sci. USA , 86 , 3753 – 3757 ( 1989. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7. ) Ikeda , I. , Ishizaka , Y. , Tahira , T. , Suzuki , T. , Sugimoto , T. , Sugimura , T. and Nagao , M.Expression of ret oncogene in human neuroblastoma cell lines . Proc. Jpn. Cancer Assoc., 47th Annu. Meet. , 222 ( 1988. ). [Google Scholar]
- 8. ) Ishizaka , Y. , Itoh , F. , Tahira , T. , Ikeda , I. , Sugimura , T. , Tucker , J. , Fertitta , A. , Carrano , A. V. and Nagao , M.Human ret proto‐oncogene mapped to chromosome 10q‐11.2 . Oncogene , 4 , 1519 – 1521 ( 1989. ). [PubMed] [Google Scholar]
- 9. ) Takahashi , M. , Buma , Y. , Iwamoto , T. , Inaguma , Y. , Ikeda , H. and Hiai , H.Cloning and expression of the ret proto‐oncogene encoding a tyrosine kinase with two potential transmembrane domains . Oncogene , 3 , 571 – 578 ( 1988. ). [PubMed] [Google Scholar]
- 10. ) Tahira , T. , Ishizaka , Y. , Itoh , F. , Sugimura , T. and Nagao , M.Characterization of ret proto‐oncogene mRNAs encoding two isoforms of the protein product in a human neuroblastoma cell line . Oncogene , 5 , 97 – 102 ( 1990. ). [PubMed] [Google Scholar]
- 11. ) Ishizaka , Y. , Ochiai , M. , Tahira , T. , Sugimura , T. and Nagao , M.Activation of the ret‐II oncogene without a sequence encoding a transmembrane domain and transforming activity of two ret‐II oncogene products differing in carboxy‐termini due to alternative splicing . Oncogene , 4 , 789 – 794 ( 1989. ). [PubMed] [Google Scholar]
- 12. ) Takahashi , M. and Cooper , G. M.retTransforming gene encodes a fusion protein homologous to tyrosine kinases . Mol. Cell. Biol. , 7 , 1378 – 1385 ( 1987. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13. ) Tahira , T. , Ishizaka , Y. , Sugimura , T. and Nagao , M.Expression of proto‐ret mRNA in embryonic and adult rat tissues . Biochem. Biophys. Res. Commun. , 153 , 1290 – 1295 ( 1988. ). [DOI] [PubMed] [Google Scholar]
- 14. ) Akiyama , S. , Fojo , A. , Hanover , J. A. , Pastan , I. and Gottesman , M. M.Isolation and genetic characterization of human KB cell lines resistant to multiple drugs . Somatic Cell Mol. Genet. , 11 , 117 – 126 ( 1985. ). [DOI] [PubMed] [Google Scholar]
- 15. ) Komiyama , S. , Matsui , K. , Kudoh , S. , Nogae , I. , Kuratomi , Y. , Sabui , Y. , Asoh , K. , Kohno , K. and Kuwano , M.Establishment of tumor cell lines from a patient with head and neck cancer and their different sensitivities to anti‐cancer agents . Cancer , 63 , 675 – 681 ( 1989. ). [DOI] [PubMed] [Google Scholar]
- 16. ) Maniatis , T. , Fritsch , E. F. and Sambrook , J. “ Molecular Cloning, A Laboratory Manual ,” p. 196 ( 1982. ). Cold Spring Harbor Laboratory Press; , New York . [Google Scholar]
- 17. ) Ishizaka , Y. , Tahira , T. , Ochiai , M. , Ikeda , I. , Sugimura , T. and Nagao , M.Molecular cloning and characterization of human ret‐II oncogene . Oncog. Res. , 3 , 193 – 197 ( 1988. ). [PubMed] [Google Scholar]
- 18. ) Schwab , M. , Alitalo , K. , Klempnauer , K‐H. , Varmus , H. E. , Bishop , J. M. , Gilbert , F. , Brodeur , G. , Goldstein , M. and Trent , J.Amplified DNA with limited homology to myc cellular oncogene is shared by human neuroblastoma cell lines and a neuroblastoma tumor . Nature , 305 , 245 – 248 ( 1983. ). [DOI] [PubMed] [Google Scholar]
- 19. ) Bongarzone , I. , Pierotti , M. A. , Monzini , N. , Mondellini , P. , Manenti , G. , Donghi , R. , Pilotti , S. , Grieco , M. , Santoro , M. , Fusco , A. , Vecchio , G. and Della Porta , G.High frequency of activation of tyrosine kinase oncogenes in human papillary thyroid carcinoma . Oncogene , 4 , 1457 – 1462 ( 1989. ). [PubMed] [Google Scholar]
- 20. ) Ishizaka , Y. , Itoh , F. , Tahira , T. , Ikeda , I. , Ogura , T. , Sugimura , T. and Nagao , M.Presence of aberrant transcripts of ret proto‐oncogene in a human papillary thyroid carcinoma cell line . Jpn. J. Cancer Res. , 80 , 1149 – 1152 ( 1989. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21. ) Nakajima‐Iijima , S. , Hamada , H. , Reddy , P. and Kakunaga , K.Molecular structure of the human cytoplasmic β‐actin gene: interspecies homology of sequences in the introns . Proc. Natl. Acad. Sci. USA , 82 , 6133 – 6137 ( 1985. ). [DOI] [PMC free article] [PubMed] [Google Scholar]