Summary
Overexpression of the nm23H1 gene has been associated with the suppression of metastasis in several solid tumors. However, in colorectal carcinoma and neuroblastoma, increased levels of nm23 H1 nucleoside diphosphate kinase A (NDPKA) mRNA are associated with tumorigenesis. To determine the role of nm23 H1/NDPKA in the prostate, normal and/or malignant tissue samples from 29 consecutive patients were studied. Levels of nm23 H1/NDPKA mRNA and nm23 H1/NDPKA mRNA protein were determined in tissue from 18 and 27 patients, respectively. In all, 16 of the 18 tumor samples expressed increased levels of nm23 H1/NDPKA mRNA as compared with those measured in normal tissue. The level of nm23 H1/NDPKA mRNA was >10-fold higher in a metastatic lymph node than in normal prostate tissue. All cancer specimens and areas of prostatic intraepithelial neoplasia showed immunoreactivity with the nm23 H1/NDPKA antibody; however, normal prostatic tissue was unreactive. These findings suggest that overexpression of the nm23 H1/NDPKA gene occurs frequently in adenocarcinomas of the prostate and may be an early event in prostate cancer tumorigenesis.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Bevilacqua G, Sobel ME, Liotta LA, Steeg PS (1989) Association of low nm23 RNA levels in human primary infiltrating ductal breast carcinomas with lymph node involvement and other histopathological indicators of high metastatic potential. Cancer Res 49:5185–5190
Boring CC, Squires TS, Tong T (1992) Cancer statistics, 1992. CA 42:19–38
Catalona WJ, Smith DS, Ratliff TL, Dodds KM, Coplen DE, Yuan JJ, Petros JA, Andriole GL (1991) Measurement of prostate-specific antigen in serum as a screening test for prostate cancer. N Engl J Med 324:1156–1161
Chomczynski P, Sacchi N (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162:156–159
Fidler IJ (1990) Critical factors in the biology of human cancer metastasis: twenty-eighth GHA Clowes Memorial Award lecture. Cancer Res 50:6130–6138
Folkman J, Klagsburn M (1987) Angiogenic factors. Science 235:442–447
Gilles AM, Presecan E, Vonica A, Lascu I (1991) Nucleoside diphosphate kinase from human erythrocytes. Structural characterization of the two polypeptide chains responsible for heterogeneity of the hexameric enzyem. J Biol Chem 266:8784–8789
Hailat N, Keim DR, Melhem RF, Zhu XX, Eckerskorn C, Brodeur GM, Reynolds CP, Seeger RC, Lottspeich F, Strahler JR, Hanash SM (1991) High levels of p19/nm23 protein in neuroblastoma are associated with advanced stage disease and with N-myc gene amplification. J Clin Invest 88:341–345
Haut M, Steeg PS, Willson JK, Markowitz SD (1991) Induction of nm23 gene expression in human colonic neoplasms and equal expression in colon tumors of high and low metastatic potential. J Natl Cancer Inst 83:712–716
Hennessy C, Henry JA, May FE, Westley BR, Angus B, Lennard TW (1991) Expression of the antimetastatic gene nm23 in human breast cancer: an association with good prognosis. J Natl Cancer Inst 83:281–285
Hirayama R, Sawai S, Takagi Y, Mishima Y, Kimura N, Shimada N, Esaki Y, Kurashima C, Utsuyama M, Hirokawa K (1991) Positive relationship between expression of antimetastatic factor (nm23 gene product or nucleoside diphosphate kinase) and good prognosis in human breast cancer. J Natl Cancer Inst 83:1249–1250
Igawa M, Rukstalis DB, Tanabe T, Chodak GW (1994) High levels of nm23 expression are related to cell proliferation in human prostate cancer. Cancer Res 54:1313–1318
Konishi N, Nakaoka S, Tsuzuki T, Matsumoto K, Kitahori Y, Hiasa Y, Urano T, Shiku H (1993) Expression of nm23-H1 and nm23-H2 proteins in prostate carcinoma. Jpn J Cancer Res 84:1050–1054
Lacombe ML, Sastre-Garau X, Lascu I, Vonica A, Wallet V, Thiery JP, Veron M (1991) Overexpression of nucleoside diphosphate kinase (nm23) in solid tumours. Eur J Cancer 27:1302–1307
Liotta LA, Stetler-Stevenson WG (1991) Tumor invasion and metastasis: an imbalance of positive and negative regulation. Cancer Res 51:5054S-5059S
Maniatis T, Fritsh EF, Sambrook J (1982) Molecular cloning: a laboratory manual. Cold Spring Harbor Laboratory, Cold Spring Harbor, New York
Miller RG Jr (1981) Survival analysis. Wiley, New York
Sawan A, Lascu I, Veron M, Anderson JJ, Wright C, Horne CW, Angus B (1993) NDP-K/nm23 expression in human breast cancer in relation to relapse, survival, and other prognostic factors: an immunohistochemical study. J Pathol 172:27–34
Stahl JA, Leone A, Rosengard AM, Porter L, King CR, Steeg PS (1991) Identification of a second human nm23 gene, nm23-H2. Cancer Res 51:445–449
Steeg PS, Bevilacqua G, Kopper L, Thorgeirsson UP, Talmadge JE, Liotta LA, Sobel ME (1988) Evidence for a novel gene associated with low tumor metastatic potential. J Natl Cancer Inst 80:200–204
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Jensen, S.L., Wood, D.P., Banks, E.R. et al. Increased levels of nm23 H1/nucleoside diphosphate kinase A mRNA associated with adenocarcinoma of the prostate. World J Urol 14, S21–S25 (1996). https://doi.org/10.1007/BF00182060
Issue Date:
DOI: https://doi.org/10.1007/BF00182060