Skip to main content
NCBI home page
Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 2000 Oct;91(10):1001–1006. doi: 10.1111/j.1349-7006.2000.tb00877.x

The Specific Expression of Three Novel Splice Variant Forms of Human Metalloprotease‐like Disintegrin‐like Cysteine‐rich Protein 2 Gene in Brain Tissues and Glioma

Taishi Harada 1, Akihiro Nishie 1, Kiyoyuki Torigoe 1, Kiyonobu Ikezaki 2, Tadahisa Shono 2, Yoshihiko Maehara 3, Michihiko Kuwano 1, Morimasa Wada 1,✉
PMCID: PMC5926265  PMID: 11050470

Abstract

We have previously identified 67 exons on a yeast artificial chromosome contig spanning 1.5 Mb around the multidrug resistance 1 gene region of human chromosome 7q21.1. In this study, we identified three novel cytoplasmic variants (MDC2‐γ, MDC2‐δ, and MDC2‐γ) of the human metalloprotease‐like disintegrin‐like cysteine‐rich protein 2 (MDC2) among these exons by screening a human brain cDNA library and also by using a reverse transcription polymerase chain reaction. Genomic sequence analysis strongly supported the idea that the variations in the cytoplasmic domain were generated by alternative splicing. The expression of MDC2 variant forms in human brain tissue and gliomas was examined by reverse transcription polymerase chain reaction and RNase protection assay. MDC2‐& ccar was expressed only in the cortical and hippocampal regions in human brain, but not in gliomas. In contrast, MDC2‐γ was a major form expressed in human gliomas. Specific expression of these cytoplasmic variants of MDC2 in human brain and its malignancies is discussed.

Keywords: MDC, ADAM, Alternative splicing, MDR region

Full Text

The Full Text of this article is available as a PDF (101.2 KB).

REFERENCES

  • 1. ) McLane , M. A. , Marcinkiewicz , C. , Vijay‐Kumar , S. , Wierzbicka‐Patynowski , I. and Niewiarowski , S.Viper venom disintegrins and related molecules . Proc. Soc. Exp. Biol. Med. , 219 , 109 – 119 ( 1993. ). [DOI] [PubMed] [Google Scholar]
  • 2. ) Myles , D. G. , Kimmel , L. H. , Blobel , C. P. , White , J. M. and Primakoff , P.Identification of a binding site in the disintegrin domain of fertilin required for sperm‐egg fusion . Proc. Natl. Acad. Sci. USA , 91 , 4195 – 4198 ( 1994. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3. ) McLeskey , S. B. , Dowds , C. , Carballada , R. , White , R. R. and Saling , P. M.Molecules involved in mammalian sperm‐egg interaction . Int. Rev. Cytol. , 177 , 57 – 113 ( 1998. ). [DOI] [PubMed] [Google Scholar]
  • 4. ) Yagami‐Hiromasa , T. , Sato , T. , Kurisaki , T. , Kamijo , K. , Nabeshima , Y. and Fujisawa‐Sehara , A.A metalloproteasedisintegrin participating in myoblast fusion . Nature , 377 , 652 – 656 ( 1995. ). [DOI] [PubMed] [Google Scholar]
  • 5. ) Moss , M. L. , Jin , S. L. , Milla , M. E. , Bickett , D. M. , Burkhart , W. , Carter , H. L. , Chen , W. J. , Clay , W. C. , Didsbury , J. R. , Hassler , D. , Hoffman , C. R. , Kost , T. A. , Lambert , M. H. , Anthony Leesnitzer , M. , McCauley , P. , McGeehan , G. , Mitchell , J. , Moyer , M. , Pahel , G. , Rocque , W. , Overton , L. K. , Schoenen , F. , Seaton , T. , Sui , J. , Warner , J. , Willard , D. and Becherer , J. D.Cloning of a disintegrin metalloproteinase that processes precursor tumour‐necrosis factor‐alpha . Nature , 385 , 733 – 736 ( 1997. ). [DOI] [PubMed] [Google Scholar]
  • 6. ) Black , R. A. , Rauch , C. T. , Kozlosky , C. J. , Peschon , J. J. , Slack , J. L. , Wolfson , M. F. , Castner , B. J. , Stocking , K. L. , Reddy , P. , Srinivasan , S. , Nelson , N. , Boiani , N. , Schooley , K. A. , Gerhart , M. , Davis , R. , Fitzner , J. N. , Johnson , R. S. , Paxton , R. J. , March , C. J. and Cerretti , D. P.A metalloproteinase disintegrin that releases tumour‐necrosis factoralpha from cells . Nature , 385 , 729 – 733 ( 1997. ). [DOI] [PubMed] [Google Scholar]
  • 7. ) Torigoe , K. , Sato , S. , Kusaba , H. , Kohno , K. , Kuwano , M. , Okumura , K. , Green , E. D. , Tsui , L. C. , Scherer , S. W. , Schlessinger , D. and Wada , M.A YAC‐based contig of 1.5 Mb spanning the human multidrug resistance gene region and delineating the amplification unit in three human multidrug‐ resistant cell lines . Genome Res. , 5 , 233 – 244 ( 1995. ). [DOI] [PubMed] [Google Scholar]
  • 8. ) Torigoe , K. , Harada , T. , Kusaba , H. , Uchiumi , T. , Kohno , K. , Green , E. D. , Scherer , S. W. , Tsui , L. C. , Schlessinger , D. , Kuwano , M. and Wada , M.Localization of 67 exons on a YAC contig spanning 1.5 Mb around the multidrug resistance gene region of human chromosome 7q21.1 . Genomics , 49 , 14 – 22 ( 1998. ). [DOI] [PubMed] [Google Scholar]
  • 9. ) Emi , M. , Katagiri , T. , Harada , Y. , Saito , H. , Inazawa , J. , Ito , I. , Kasumi , F. and Nakamura , Y.A novel metalloprotease/disintegrin‐like gene at 17q21.3 is somatically rearranged in two primary breast cancers . Nat. Genet. , 5 , 151 – 157 ( 1993. ). [DOI] [PubMed] [Google Scholar]
  • 10. ) Katagiri , T. , Harada , Y. , Emi , M. and Nakamura , Y.Human metalloprotease/disintegrin‐like (MDC) gene: exonintron organization and alternative splicing . Cytogenet. Cell Genet. , 68 , 39 – 44 ( 1995. ). [DOI] [PubMed] [Google Scholar]
  • 11. ) Sagane , K. , Ohya , Y. , Hasegawa , Y. and Takano , I.Metalloproteinase‐like, disintegrin‐like, cysteine‐rich proteins MDC2 and MDC3: novel human cellular disintegrins highly expressed in the brain . Biochem. J. , 334 , 93 – 98 ( 1998. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12. ) Abe , T. , Okamura , K. , Ono , M. , Kohno , K. , Mori , T. , Hori , S. and Kuwano , M.Induction of vascular endothelial tubular morphogenesis by human glioma cells. A model system for tumor angiogenesis . J. Clin. Invest. , 92 , 54 – 61 ( 1993. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13. ) Padgett , R. A. , Grabowski , P. J. , Konarska , M. M. , Seiler , S. and Sharp , P. A.Splicing of messenger RNA precursors . Annu. Rev. Biochem. , 55 , 1119 – 1150 ( 1986. ). [DOI] [PubMed] [Google Scholar]
  • 14. ) Wu , Q. and Krainer , R. A.U1‐mediated exon definition interactions between AT‐AC and GT‐AG introns . Science , 274 , 1005 – 1008 ( 1996. ). [DOI] [PubMed] [Google Scholar]
  • 15. ) Cavabgh , J. B. and Meyer , A.Etiological aspects of Ammon's horn sclerosis associated with temporal lobe epilepsy . Br. Med. J. , 2 , 1403 – 1407 ( 1956. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16. ) Meyer , A. , Falconer , M. A. and Beck , E.Pathological findings in temporal lobe epilepsy . J. Neurol. Neurosurg. Psychiatry , 17 , 276 – 285 ( 1954. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17. ) Magerison , J. H. and Corsellis , J. A. N.Epilepsy and the temporal lobes . Brain , 89 , 499 – 530 ( 1966. ). [DOI] [PubMed] [Google Scholar]
  • 18. ) Mouritzen Dam , A.Epilepsy and neuron loss in the hippocampus . Epilepsia , 21 , 617 – 629 ( 1980. ). [DOI] [PubMed] [Google Scholar]
  • 19. ) Black , R. A. and White , J. M.ADAMs: focus on the protease domain . Curr. Opin. Cell Biol. , 10 , 654 – 659 ( 1998. ). [DOI] [PubMed] [Google Scholar]
  • 20. ) Gonzalez , A. F. , Raden , L. D. and Davis , R. J.Identification of substrate recognition determinants for human ERK1 and ERK2 protein kinase . J. Biol. Chem. , 266 , 22159 – 22163 ( 1991. ). [PubMed] [Google Scholar]
  • 21. ) Songyang , Z. , Fanning , A. S. , Fu , C. , Xu , J. , Marfatia , S. M. , Chishti , A. H. , Crompton , A. , Chan , A. C. , Anderson , J. M. and Cantley , L. C.Recognition of unique carboxylterminal motif by distinct PDZ domains . Science , 275 , 73 – 77 ( 1997. ). [DOI] [PubMed] [Google Scholar]

Articles from Japanese Journal of Cancer Research : Gann are provided here courtesy of Wiley

RESOURCES