Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1997;76(9):1199–1204. doi: 10.1038/bjc.1997.533

Overexpression of hepatic prothymosin alpha, a novel marker for human hepatocellular carcinoma.

C G Wu 1, N A Habib 1, R R Mitry 1, P H Reitsma 1, S J van Deventer 1, R A Chamuleau 1
PMCID: PMC2228121  PMID: 9365169

Abstract

Identification of gene products exclusively or abundantly expressed in cancer may yield novel tumour markers. We recently isolated a number of cDNA clones, including alpha-prothymosin, from rat hepatocellular carcinoma (HCC) using a subtraction-enhanced display technique. Alpha-Prothymosin is involved in cell proliferation and is regulated by the oncogene c-myc in vitro. In the present study, we analysed alpha-prothymosin gene expression and its correlation with c-myc in patients with HCC, cirrhosis and adenoma and in normal controls. Hepatic alpha-prothymosin messenger RNA (mRNA) levels were two- to 9.2-fold higher in tumoral tissues than in adjacent non-tumoral tissues in 14 of 17 patients with HCC, regardless of coexisting cirrhosis and viral hepatitis. No marked difference in alpha-prothymosin mRNA levels was present in patients with adenoma and hepatic cirrhosis and in healthy controls. The c-myc mRNA amounts were two- to fivefold increased in 11 of 17 patients with HCC and correlated significantly with those of alpha-prothymosin (P < 0.001). In situ hybridization revealed that increased alpha-prothymosin mRNA was localized in the tumour nodules of the patients with HCC. These data suggest that overexpression of alpha-prothymosin in HCC patients, correlated with c-myc, is possibly involved in the tumorigenic process and may be a novel molecular marker for human HCC.

Full text

PDF
1199

Images in this article

1201Figure 1
on p.1201
1201Figure 2
on p.1201
1202Figure 5
on p.1202

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aihara T., Noguchi S., Sasaki Y., Nakano H., Monden M., Imaoka S. Clonal analysis of precancerous lesion of hepatocellular carcinoma. Gastroenterology. 1996 Aug;111(2):455–461. doi: 10.1053/gast.1996.v111.pm8690212. [DOI] [PubMed] [Google Scholar]
  2. Caselmann W. H. Transactivation of cellular gene expression by hepatitis B viral proteins: a possible molecular mechanism of hepatocarcinogenesis. J Hepatol. 1995;22(1 Suppl):34–37. [PubMed] [Google Scholar]
  3. Chandar N., Lombardi B., Locker J. c-myc gene amplification during hepatocarcinogenesis by a choline-devoid diet. Proc Natl Acad Sci U S A. 1989 Apr;86(8):2703–2707. doi: 10.1073/pnas.86.8.2703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chen D. S., Sung J. L., Sheu J. C., Lai M. Y., How S. W., Hsu H. C., Lee C. S., Wei T. C. Serum alpha-fetoprotein in the early stage of human hepatocellular carcinoma. Gastroenterology. 1984 Jun;86(6):1404–1409. [PubMed] [Google Scholar]
  5. Colombo M., de Franchis R., Del Ninno E., Sangiovanni A., De Fazio C., Tommasini M., Donato M. F., Piva A., Di Carlo V., Dioguardi N. Hepatocellular carcinoma in Italian patients with cirrhosis. N Engl J Med. 1991 Sep 5;325(10):675–680. doi: 10.1056/NEJM199109053251002. [DOI] [PubMed] [Google Scholar]
  6. Dominguez F., Magdalena C., Cancio E., Roson E., Paredes J., Loidi L., Zalvide J., Fraga M., Forteza J., Regueiro B. J. Tissue concentrations of prothymosin alpha: a novel proliferation index of primary breast cancer. Eur J Cancer. 1993;29A(6):893–897. doi: 10.1016/s0959-8049(05)80433-2. [DOI] [PubMed] [Google Scholar]
  7. Du W., Xie J. E., Dyson N. Ectopic expression of dE2F and dDP induces cell proliferation and death in the Drosophila eye. EMBO J. 1996 Jul 15;15(14):3684–3692. [PMC free article] [PubMed] [Google Scholar]
  8. Eilers M., Schirm S., Bishop J. M. The MYC protein activates transcription of the alpha-prothymosin gene. EMBO J. 1991 Jan;10(1):133–141. doi: 10.1002/j.1460-2075.1991.tb07929.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Eschenfeldt W. H., Berger S. L. The human prothymosin alpha gene is polymorphic and induced upon growth stimulation: evidence using a cloned cDNA. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9403–9407. doi: 10.1073/pnas.83.24.9403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gan F. Y., Gesell M. S., Alousi M., Luk G. D. Analysis of ODC and c-myc gene expression in hepatocellular carcinoma by in situ hybridization and immunohistochemistry. J Histochem Cytochem. 1993 Aug;41(8):1185–1196. doi: 10.1177/41.8.7687263. [DOI] [PubMed] [Google Scholar]
  11. Garte S. J. The c-myc oncogene in tumor progression. Crit Rev Oncog. 1993;4(4):435–449. [PubMed] [Google Scholar]
  12. Gaubatz S., Meichle A., Eilers M. An E-box element localized in the first intron mediates regulation of the prothymosin alpha gene by c-myc. Mol Cell Biol. 1994 Jun;14(6):3853–3862. doi: 10.1128/mcb.14.6.3853. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Haritos A. A., Goodall G. J., Horecker B. L. Prothymosin alpha: isolation and properties of the major immunoreactive form of thymosin alpha 1 in rat thymus. Proc Natl Acad Sci U S A. 1984 Feb;81(4):1008–1011. doi: 10.1073/pnas.81.4.1008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hsieh L. L., Shinozuka H., Weinstein I. B. Changes in expression of cellular oncogenes and endogenous retrovirus-like sequences during hepatocarcinogenesis induced by a peroxisome proliferator. Br J Cancer. 1991 Nov;64(5):815–820. doi: 10.1038/bjc.1991.406. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Johnson P. J., Williams R. Cirrhosis and the aetiology of hepatocellular carcinoma. J Hepatol. 1987 Feb;4(1):140–147. doi: 10.1016/s0168-8278(87)80021-1. [DOI] [PubMed] [Google Scholar]
  16. Land H., Parada L. F., Weinberg R. A. Cellular oncogenes and multistep carcinogenesis. Science. 1983 Nov 18;222(4625):771–778. doi: 10.1126/science.6356358. [DOI] [PubMed] [Google Scholar]
  17. Lasserre C., Christa L., Simon M. T., Vernier P., Bréchot C. A novel gene (HIP) activated in human primary liver cancer. Cancer Res. 1992 Sep 15;52(18):5089–5095. [PubMed] [Google Scholar]
  18. Mol P. C., Wang R. H., Batey D. W., Lee L. A., Dang C. V., Berger S. L. Do products of the myc proto-oncogene play a role in transcriptional regulation of the prothymosin alpha gene? Mol Cell Biol. 1995 Dec;15(12):6999–7009. doi: 10.1128/mcb.15.12.6999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Mori M., Barnard G. F., Staniunas R. J., Jessup J. M., Steele G. D., Jr, Chen L. B. Prothymosin-alpha mRNA expression correlates with that of c-myc in human colon cancer. Oncogene. 1993 Oct;8(10):2821–2826. [PubMed] [Google Scholar]
  20. Nagy P., Evarts R. P., Marsden E., Roach J., Thorgeirsson S. S. Cellular distribution of c-myc transcripts during chemical hepatocarcinogenesis in rats. Cancer Res. 1988 Oct 1;48(19):5522–5527. [PubMed] [Google Scholar]
  21. Sburlati A. R., Manrow R. E., Berger S. L. Prothymosin alpha antisense oligomers inhibit myeloma cell division. Proc Natl Acad Sci U S A. 1991 Jan 1;88(1):253–257. doi: 10.1073/pnas.88.1.253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Sharara A. I., Hunt C. M., Hamilton J. D. Hepatitis C. Ann Intern Med. 1996 Oct 15;125(8):658–668. doi: 10.7326/0003-4819-125-8-199610150-00006. [DOI] [PubMed] [Google Scholar]
  23. Sinha S., Webber C., Marshall C. J., Knowles M. A., Proctor A., Barrass N. C., Neal G. E. Activation of ras oncogene in aflatoxin-induced rat liver carcinogenesis. Proc Natl Acad Sci U S A. 1988 Jun;85(11):3673–3677. doi: 10.1073/pnas.85.11.3673. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Vareli K., Tsolas O., Frangou-Lazaridis M. Regulation of prothymosin alpha during the cell cycle. Eur J Biochem. 1996 Jun 15;238(3):799–806. doi: 10.1111/j.1432-1033.1996.0799w.x. [DOI] [PubMed] [Google Scholar]
  25. Wands J. R., Blum H. E. Primary hepatocellular carcinoma. N Engl J Med. 1991 Sep 5;325(10):729–731. doi: 10.1056/NEJM199109053251010. [DOI] [PubMed] [Google Scholar]
  26. Wepsic H. T., Kirkpatrick A. Alpha-fetoprotein and its relevance to human disease. Gastroenterology. 1979 Oct;77(4 Pt 1):787–796. [PubMed] [Google Scholar]
  27. Wu C. G., Groenink M., Bosma A., Reitsma P. H., van Deventer S. J., Chamuleau R. A. Rat ferritin-H: cDNA cloning, differential expression and localization during hepatocarcinogenesis. Carcinogenesis. 1997 Jan;18(1):47–52. doi: 10.1093/carcin/18.1.47. [DOI] [PubMed] [Google Scholar]
  28. Wu C. G., Hakvoort T. B., Lamers W. H., Chamuleau R. A. Isolation of up- and down-regulated cDNAs associated with hepatocellular carcinoma by a subtraction-enhanced display technique. Biochim Biophys Acta. 1996 Apr 12;1315(3):169–175. doi: 10.1016/0925-4439(95)00117-4. [DOI] [PubMed] [Google Scholar]
  29. Zatz M. M., Goldstein A. L. Thymosins, lymphokines, and the immunology of aging. Gerontology. 1985;31(4):263–277. doi: 10.1159/000212709. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES