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. 1994 Jan;85(1):32–39. doi: 10.1111/j.1349-7006.1994.tb02883.x

Abundant but Inactive‐state gpl40prototrk Is Expressed in Neuroblastomas of Patients with Good Prognosis

Hiroyuki Iwata 1, Takahiro Ito 1, Tatsuro Mutoh 2, Yukio Ishiguro 1, Hengyi Xiao 3, Michinari Hamaguchi 3,✉
PMCID: PMC5919340  PMID: 7508904

Abstract

Steady‐state levels of gp140proto‐trk in cell lines and tumor tissues of neurohlastoma were examined by immunoblotting with anti‐gpl40proto‐trk The level of gpl40proto‐trk varied but showed good correlations with the stage of the tumor and the age of the patients at the time of diagnosis. Moreover, patients with higher expression of gpl40proto‐trk clearly had a far better survival rate than those with lower expression, suggesting that suppression of gp140proto‐trkstrongly correlates with the malignant conversion of the tumor. However, we found that neither autophosphorylation of gpl40proto‐trknor tyrosine phosphoryla‐tion of cellular proteins was elevated in tumors of the higher expression group. These results suggest that gpl40proto‐trk does not actively participate in the process of transformation or the suppression of malignant conversion. Rather, the higher level of gpl40proto‐trkmay reflect the greater level of differentiation of tumor cells.

Keywords: trk ‐gpl40proto‐trk, Tyrosine kinase, Neuroblastoma, Prognosis marker

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REFERENCES

  • 1. ) Evans , A. E.Natural history of neuroblastoma . Adv. Neuroblastoma Res. , 3 – 12 ( 1980. ).
  • 2. ) Evans , A. E. , D'Angio , G. J. and Randolph , J. A.A proposed staging for children with neuroblastoma . Cancer , 27 , 374 – 378 ( 1971. ). [DOI] [PubMed] [Google Scholar]
  • 3. ) D'Angio , G. J. , Evans , A. E. and Koop , C. E.Special pattern of widespread neuroblastoma with a favorable prognosis . Lancet , i , 1046 – 1049 ( 1971. ). [DOI] [PubMed] [Google Scholar]
  • 4. ) Evans , A. E. , Baum , E. and Chard , R.Do infants with stage IV‐s neuroblastoma need treatment ? Arch. Dis. Child. , 56 , 271 – 274 ( 1981. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5. ) Breslow , N. and McCann , B.Statistical estimation of prognosis for children with neuroblastoma . Cancer Res. , 31 , 2098 – 2103 ( 1971. ). [PubMed] [Google Scholar]
  • 6. ) Kinnier Wilson , L. M. K. and Draper , G. J.Neuroblastoma, its natural history and prognosis: a study of 487 cases . Br. Med. J. , 3 , 301 – 307 ( 1974. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7. ) Moss , T. J. , Fonkalsrud , E. W. , Feig , S. A. , Lenarsky , C. , Selch , M. , Wells , J. and Seeger , R. C.Delayed surgery and bone marrow transplantation for widespread neuroblastoma . Ann. Surg. , 206 , 514 – 518 ( 1987. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8. ) Kohl , N. E. , Kanda , N. , Schreck , R. R. , Bruns , G. , Latt , S. A. , Gilbert , F. and Alt , F. W.Transposition and amplification of oncogene‐related sequences in human neuroblastoma . Cell , 35 , 359 – 367 ( 1983. ). [DOI] [PubMed] [Google Scholar]
  • 9. ) Brodeur , G. M. , Seeger , R. C. , Schwab , M. , Varmus , H. E. and Bishop , J. M.Amplification of N‐myc in untreated human neuroblastomas correlates with advanced disease stage . Science , 224 , 1121 – 1124 ( 1984. ). [DOI] [PubMed] [Google Scholar]
  • 10. ) Johnson , D. , Lanahanm , A. A. , Buck , C. R. , Sehgal , A. , Morgan , C. , Mercer , E. , Bothwell , M. A. and Chao , M. V.Expression and structure of the human NGF receptor . Cell. 47 , 545 – 554 ( 1986. ). [DOI] [PubMed] [Google Scholar]
  • 11. ) Kaplan , D. R. , Hempstead , B. L. , Martin‐Zanca , D. , Chao , M. V. and Parada , L. F.The irk proto‐oncogene product: a signal transducing receptor for nerve growth factor . Science , 252 , 554 – 558 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 12. ) Suzuki , T. , Bogenmann , E. , Shimada , H. , Stram , D. and Seeger , R. C.Lack of high affinity nerve growth factor receptors in aggressive neuroblastomas . J. Natl. Cancer Inst , 85 , 377 – 384 ( 1993. ). [DOI] [PubMed] [Google Scholar]
  • 13. ) Nakagawara , A. , Arima‐Nakagawara , M. , Scavarda , N. J. , Azar , C. G. , Cantor , A. B. and Brodeur , G. M.Association between high levels of expression of the trk gene and favorable outcome in human neuroblastoma . N. Engl J. Med. , 328 , 847 – 854 ( 1993. ). [DOI] [PubMed] [Google Scholar]
  • 14. ) Marin‐Zanca , D. , Oskam , R. , Mitra , G. , Copeland , T. and Barbacid , M.Molecular and biochemical characterization of the human trk proto‐oncogene . Mol. Cell. Biol , 9 , 24 – 33 ( 1989. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15. ) Mutoh , T. , Tokuda , A. , Guroff , G. and Fujiki , N.The effect of the B subunit of cholera toxin on the action of nerve growth factor on PC 12 cells . J. Neurochem. ( 1993. ), in press . [DOI] [PubMed]
  • 16. ) Wang , J. Y. J.Isolation of antibodies for phosphotyrosine by immunization with a v‐abl oncogene‐encoded protein . Mol. Cell. Biol , 5 , 3640 – 3643 ( 1985. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17. ) Hamaguchi , M. , Grandori , C. and Hanafusa , H.Phosphorylation of cellular proteins in Rous sarcoma virus‐infected cells: analysis by use of anti‐phosphotyrosine antibodies . Mol. Cell. Biol , 8 , 3035 – 3042 ( 1988. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18. ) Hamaguchi , M. and Hanafusa , H.Association of p60STC with Triton X‐100‐resistant cellular structure correlates with morphological transformation . Proc. Natl Acad. Sci. USA , 84 , 2312 – 2316 ( 1987. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19. ) Hamaguchi , M. , Matsuyoshi , N. , Ohnishi , Y. , Gotoh , B. , Takeichi , M. and Nagai , Y.p60v‐srccauses tyrosine phos‐phorylation and inactivation of the N‐cadherin‐catenin cell adhesion system . EMBO J. , 12 , 307 – 314 ( 1993. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20. ) Ellis , C. , Moran , M. , McCormick , F. and Pawson , T.Phosphorylation of GAP and GAP‐associated proteins by transforming and mitogenic tyrosine kinases . Nature , 343 , 377 – 380 ( 1990. ). [DOI] [PubMed] [Google Scholar]
  • 21. ) Kaneko , M. and Tsuchida , Y.Prognosis analysis for neuroblastoma based on clinical data of the Study Group of Japan for Advanced Neuroblastoma . Jpn. J. Pediatr. Surg. , 23 , 431 – 437 ( 1991. ) ( in Japanese ). [Google Scholar]
  • 22. ) Christansen , H. , Christiansen , N. M. , Wagner , F. , Altmannsberger , M. and Lampert , F.Neuroblastoma: inverse relationship between expression of N‐myc and NGF‐r . Oncogene , 5 , 437 – 440 ( 1990. ). [PubMed] [Google Scholar]
  • 23. ) Nakagawara , A. , Arima , M. , Azar , C. G. , Scavarda , N. J. and Brodeur , G. M.Inverse relationship between trk expression and N‐myc amplification in human neuroblas‐tomas . Cancer Res. , 52 , 1364 – 1368 ( 1992. ). [PubMed] [Google Scholar]
  • 24. ) 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 . JV. Engl. J. Meet , 313 , 1111 – 1116 ( 1985. ). [DOI] [PubMed] [Google Scholar]
  • 25. ) Martin‐Zanca , D. , Hughes , S. H. and Barbacid , M.A human oncogene formed by the fusion of truncated tropo‐myosin and protein tyrosine kinase sequences . Nature , 319 , 743 – 748 ( 1986. ). [DOI] [PubMed] [Google Scholar]
  • 26. ) Beckwith , J. B. and Perrin , E. V.In situ neuroblastomas: a contribution to the natural history of neural crest tumors . Am. J. Pathol , 43 , 1089 – 1104 ( 1963. ). [PMC free article] [PubMed] [Google Scholar]
  • 27. ) Sidell , N. , Altmann , A. , Haussler , M. R. and Seeger , R. C.Effects of retinoic acid (RA) on the growth and phenotypic expression of several human neuroblastoma cell lines . Exp. Cell Res. , 148 , 21 – 30 ( 1983. ). [DOI] [PubMed] [Google Scholar]
  • 28. ) Aza , C. , Scavarda , N. J. , Reynolds , C. P. and Brodeur , G. M.Multiple defects of the nerve growth factor receptor in human neuroblastomas . Cell Growth Differ. , 1 , 421 – 428 ( 1990. ). [PubMed] [Google Scholar]
  • 29. ) Huff , K. , End , D. and Guroff , G.Nerve growth factor‐induced alteration in the response of PC 12 pheochromo‐cytoma cells to epidermal growth factor . J. Cell Biol , 88 , 189 – 198 ( 1981. ). [DOI] [PMC free article] [PubMed] [Google Scholar]

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