Journal of Gastroenterology

, Volume 29, Issue 6, pp 727–732 | Cite as

Expression of cytoskeletal-associated protein tyrosine phosphatase PTPH1 mRNA in human hepatocellular carcinoma

  • Shigeo Ikuta
  • Fumio Itoh
  • Yuji Hinoda
  • Minoru Toyota
  • Yusuke Makiguchi
  • Kohzoh Imai
  • Akira Yachi
Liver, Pancreas, and Biliary Tract


We investigated the mRNA expression of cytosolic protein tyrosine phosphatase (PTPH1), which has a homologous domain to cytoskeletal-associated proteins, in human hepatocellular carcinomas (HCCs) by using reverse transcriptase-polymerase chain reaction (RT-PCR). PTPH1 mRNA was detected in all HCC cell lines (n=6), and HCC and adjacent noncancerous tissues (n=8) examined, indicating that PTPH1 was expressed in HCCs and hepatocytes. There was no remarkable difference in the level expression of PTPH1 mRNA between HCC and adjacent noncancerous tissues. We also performed RT-PCR single-strand conformation polymorphism (SSCP) analysis in HCC cell lines and tissues in the C-terminal region of the catalytic domain of PTPH1. In the cHc4 cell line and a HCC tissue specimen, a shifted band was detected, although it was not found in the noncancerous tissue of the HCC specimen. Nucleotide sequence analysis showed a common mutation from T to C at the third letter of codon 919 which did not lead to amino acid substitution. These results suggest that another mutation leading to the development of HCC could occur in some region of PTPH1 other than that investigated in this study.

Key words

protein tyrosine phosphatase PTPH1 RT-PCR RT-PCR SSCP hepatocellular carcinoma 


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  1. 1.
    Fearon ER, Vogelstein B. A genetic model for colorectal tumorigenesis. Cell 1990;61:759–767.CrossRefPubMedGoogle Scholar
  2. 2.
    Vogelstein B, Fearon ER, Hamilton SR, et al. Genetic alterations during colorectal tumor development. N Engl J Med 1988; 319:525–532.PubMedGoogle Scholar
  3. 3.
    Kinzler KW, Nilbert MC, Su LK, et al. Identification of FAP locus gene from chromosome 5q21. Science 1991;253:661–665.PubMedGoogle Scholar
  4. 4.
    Fearon ER, Cho KR, Nigro JM, et al. Identification of a chromosome 18q gene that is altered in colorectal cancers. Seience 1990;247:49–56.Google Scholar
  5. 5.
    Baker SJ, Fearon ER, Nigro JM, et al. Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas. Science 1989;244:217–221.PubMedGoogle Scholar
  6. 6.
    Zhang W, Hirohashi S, Tsuda H, et al. Frequent loss of heterozygosity on chromosomes 16 and 4 in human hepatocellular carcinoma. Jpn J Cancer Res 1990;81:108–111.PubMedGoogle Scholar
  7. 7.
    Sakamoto M, Hirohashi S, Shimosato Y. Early stages of multistep hepatocarcinogenesis. Hum Pathol 1991;22:172–178.CrossRefPubMedGoogle Scholar
  8. 8.
    Pot DA, Dixon JE. A thousand and two protein tyrosine phosphatases. Biochim Biophys Acta 1992;1136:35–43.PubMedGoogle Scholar
  9. 9.
    LaForgia S, Morse B, Levy J, et al. Receptor protein-tyrosine phosphatase is a candidate tumor suppressor gene at human chromosome region 3p21. Proc Natl Acad Sci USA 1991;88: 5036–5040.PubMedGoogle Scholar
  10. 10.
    Arimura Y, Hinoda H, Itoh F, et al. cDNA cloning of new human protein tyrosine phosphatases in the human colon. Tumor Biol 1992;13:180–186.Google Scholar
  11. 11.
    Yang Q, Tonks NK. Isolation of a cDNA clone encoding a human protein-tyrosine phosphatase with homology to the cytoskeletal-associated proteins band 4.1, ezrin, and talin Proc Natl Acad Sci USA 1991;88:5949–5953.PubMedGoogle Scholar
  12. 12.
    Rouleau GA, Merel P, Lutchman M, et al. Alteration in a new gene encoding a putative membrane-organizing protein causes neurofibromatosis type 2. Nature 1993;363:515–521.CrossRefPubMedGoogle Scholar
  13. 13.
    Itoh F, Ikuta S, Hinoda Y, et al. Expression and chromosomal assignment of PTPH1 gene encoding a cytosolic protein tyrosine phosphatase homologous to cytoskeletal associated proteins. Int J Cancer 1993;55:947–951.PubMedGoogle Scholar
  14. 14.
    Chomczynski P, Sacchi N. Singe-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 1987;162:156–159.CrossRefPubMedGoogle Scholar
  15. 15.
    Saiki RK, Scharf S, Faloona F, et al. Enzymatic amplification of β-globin genomic sequences and restriction-site analysis for diagnosis of sickle-cell anemia. Science 1985;230:1350–1354.PubMedGoogle Scholar
  16. 16.
    Sanger F, Nicklen S, Coulson AR. DNA sequencing with chainterminating inhibitor. Proc Natl Acad Sci USA 1977;74:5463–5467.PubMedGoogle Scholar
  17. 17.
    Brautigan DL. Great expectations: Protein tyrosine phosphatases in cell regulation. Biochim Biophys Acta 1992;1114:63–77.PubMedGoogle Scholar
  18. 18.
    Gu M, York JD, Warshawsky I, Majerus PW. Identification, cloning, and expression of a cytosolic megakaryocyte protein-tyrosine-phosphatase with sequence homology to cytoskeletal protein 4.1. Proc Natl Acad Sci USA 1991;88:5867–5871.PubMedGoogle Scholar
  19. 19.
    Itoh F, Hinoda Y, Ohe M, et al. Decreased expression of DCC mRNA in human colorectal cancers. Int J Cancer 1993;53:260–263.PubMedGoogle Scholar
  20. 20.
    Yoshimoto M, Itoh F, Yamamoto H, et al. Expression of MMP-7 (pump-1) mRNA in human colorectal cancers. Int J Cancer 1993;54:614–618.PubMedGoogle Scholar
  21. 21.
    Nishi M, Ohagi S, Steiner D. Novel putative protein tyrosine phosphatases identified by the polymerase chain reaction. FEBS Lett 1990;271:178–180.CrossRefPubMedGoogle Scholar
  22. 22.
    Sekido Y, Takahashi T, Ueda R, et al. Recombinant human stem cell factor mediates chemotaxis of small-cell lung cancer cell lines aberrantly expressing thec-kit protooncogene. Cancer Res 1993;53:1709–1714.PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1994

Authors and Affiliations

  • Shigeo Ikuta
    • 1
  • Fumio Itoh
    • 1
  • Yuji Hinoda
    • 1
  • Minoru Toyota
    • 1
  • Yusuke Makiguchi
    • 1
  • Kohzoh Imai
    • 1
  • Akira Yachi
    • 1
  1. 1.Department of Internal Medicine (Section 1), School of MedicineSapporo Medical UniversitySapporoJapan

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