Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1990 Sep;86(3):900–908. doi: 10.1172/JCI114791

Acetylcholinesterase and butyrylcholinesterase genes coamplify in primary ovarian carcinomas.

H Zakut 1, G Ehrlich 1, A Ayalon 1, C A Prody 1, G Malinger 1, S Seidman 1, D Ginzberg 1, R Kehlenbach 1, H Soreq 1
PMCID: PMC296809  PMID: 2394839

Abstract

The genes for acetylcholinesterase (ACHE) and butyrylcholinesterase (CHE) are expressed in multiple tumor tissues, including ovarian carcinomas. Both CHE and ACHE genes coamplify in leukemias. To examine the relationship of gene amplification to the expression of these genes in tumors, ACHE and CHE genes and their expression were studied in primary ovarian carcinomas. DNA blot hybridization demonstrated a significant amplification and mutagenesis of both genes in 6 of 11 malignant tumors studied. This was greater or of the same order of magnitude as the amplification of the oncogenes c-rafi, v-sis, and c-fes in these tumors. No amplification was found in normal ovarian tissues or benign ovarian cysts. Xenopus oocyte microinjections, blot and in situ hybridizations, and immuno- and cytochemical staining revealed translatable CHEmRNA and its active protein product in discrete tumor foci. The frequent coamplification in ovarian carcinomas of ACHE and CHE genes implicates cholinesterases in neoplastic growth and/or proliferation.

Full text

PDF
900

Images in this article

901Image
on p.901
902Image
on p.902
902Image
on p.902
902Image
on p.902
904Image
on p.904
905Image
on p.905
906Image
on p.906
906Image
on p.906
906Image
on p.906
906Image
on p.906

Selected References

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

  1. Ahmed F. E., Hart R. W., Lewis N. J. Pesticide induced DNA damage and its repair in cultured human cells. Mutat Res. 1977 Feb;42(2):161–174. doi: 10.1016/s0027-5107(77)80020-1. [DOI] [PubMed] [Google Scholar]
  2. Bishop J. M. The molecular genetics of cancer. Science. 1987 Jan 16;235(4786):305–311. doi: 10.1126/science.3541204. [DOI] [PubMed] [Google Scholar]
  3. Chatonnet A., Lockridge O. Comparison of butyrylcholinesterase and acetylcholinesterase. Biochem J. 1989 Jun 15;260(3):625–634. doi: 10.1042/bj2600625. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Drews U. Cholinesterase in embryonic development. Prog Histochem Cytochem. 1975;7(3):1–52. [PubMed] [Google Scholar]
  5. Dreyfus P. A., Seidman S., Pincon-Raymond M., Murawsky M., Rieger F., Schejter E., Zakut H., Soreq H. Tissue-specific processing and polarized compartmentalization of clone-produced cholinesterase in microinjected Xenopus oocytes. Cell Mol Neurobiol. 1989 Sep;9(3):323–341. doi: 10.1007/BF00711413. [DOI] [PubMed] [Google Scholar]
  6. Dreyfus P., Zevin-Sonkin D., Seidman S., Prody C., Zisling R., Zakut H., Soreq H. Cross-homologies and structural differences between human cholinesterases revealed by antibodies against cDNA-produced human butyrylcholinesterase peptides. J Neurochem. 1988 Dec;51(6):1858–1867. doi: 10.1111/j.1471-4159.1988.tb01169.x. [DOI] [PubMed] [Google Scholar]
  7. Gnatt A., Prody C. A., Zamir R., Lieman-Hurwitz J., Zakut H., Soreq H. Expression of alternatively terminated unusual human butyrylcholinesterase messenger RNA transcripts, mapping to chromosome 3q26-ter, in nervous system tumors. Cancer Res. 1990 Apr 1;50(7):1983–1987. [PubMed] [Google Scholar]
  8. Király J., Szentesi I., Ruzicska M., Czeize A. Chromosome studies in workers producing organophosphate insecticides. Arch Environ Contam Toxicol. 1979;8(3):309–319. doi: 10.1007/BF01056247. [DOI] [PubMed] [Google Scholar]
  9. Kohl N. E., Kanda N., Schreck R. R., Bruns G., Latt S. A., Gilbert F., Alt F. W. Transposition and amplification of oncogene-related sequences in human neuroblastomas. Cell. 1983 Dec;35(2 Pt 1):359–367. doi: 10.1016/0092-8674(83)90169-1. [DOI] [PubMed] [Google Scholar]
  10. Lapidot-Lifson Y., Prody C. A., Ginzberg D., Meytes D., Zakut H., Soreq H. Coamplification of human acetylcholinesterase and butyrylcholinesterase genes in blood cells: correlation with various leukemias and abnormal megakaryocytopoiesis. Proc Natl Acad Sci U S A. 1989 Jun;86(12):4715–4719. doi: 10.1073/pnas.86.12.4715. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Layer P. G., Alber R., Sporns O. Quantitative development and molecular forms of acetyl- and butyrylcholinesterase during morphogenesis and synaptogenesis of chick brain and retina. J Neurochem. 1987 Jul;49(1):175–182. doi: 10.1111/j.1471-4159.1987.tb03411.x. [DOI] [PubMed] [Google Scholar]
  12. Layer P. G., Sporns O. Spatiotemporal relationship of embryonic cholinesterases with cell proliferation in chicken brain and eye. Proc Natl Acad Sci U S A. 1987 Jan;84(1):284–288. doi: 10.1073/pnas.84.1.284. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Malinger G., Zakut H., Soreq H. Cholinoceptive properties of human primordial, preantral, and antral oocytes: in situ hybridization and biochemical evidence for expression of cholinesterase genes. J Mol Neurosci. 1989;1(2):77–84. doi: 10.1007/BF02896891. [DOI] [PubMed] [Google Scholar]
  14. McGuire M. C., Nogueira C. P., Bartels C. F., Lightstone H., Hajra A., Van der Spek A. F., Lockridge O., La Du B. N. Identification of the structural mutation responsible for the dibucaine-resistant (atypical) variant form of human serum cholinesterase. Proc Natl Acad Sci U S A. 1989 Feb;86(3):953–957. doi: 10.1073/pnas.86.3.953. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. McTiernan C., Adkins S., Chatonnet A., Vaughan T. A., Bartels C. F., Kott M., Rosenberry T. L., La Du B. N., Lockridge O. Brain cDNA clone for human cholinesterase. Proc Natl Acad Sci U S A. 1987 Oct;84(19):6682–6686. doi: 10.1073/pnas.84.19.6682. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Mouchès C., Pasteur N., Bergé J. B., Hyrien O., Raymond M., de Saint Vincent B. R., de Silvestri M., Georghiou G. P. Amplification of an esterase gene is responsible for insecticide resistance in a California Culex mosquito. Science. 1986 Aug 15;233(4765):778–780. doi: 10.1126/science.3755546. [DOI] [PubMed] [Google Scholar]
  17. Møllgård K., Dziegielewska K. M., Saunders N. R., Zakut H., Soreq H. Synthesis and localization of plasma proteins in the developing human brain. Integrity of the fetal blood-brain barrier to endogenous proteins of hepatic origin. Dev Biol. 1988 Jul;128(1):207–221. doi: 10.1016/0012-1606(88)90283-7. [DOI] [PubMed] [Google Scholar]
  18. Prody C. A., Dreyfus P., Zamir R., Zakut H., Soreq H. De novo amplification within a "silent" human cholinesterase gene in a family subjected to prolonged exposure to organophosphorous insecticides. Proc Natl Acad Sci U S A. 1989 Jan;86(2):690–694. doi: 10.1073/pnas.86.2.690. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Prody C. A., Zevin-Sonkin D., Gnatt A., Goldberg O., Soreq H. Isolation and characterization of full-length cDNA clones coding for cholinesterase from fetal human tissues. Proc Natl Acad Sci U S A. 1987 Jun;84(11):3555–3559. doi: 10.1073/pnas.84.11.3555. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Rakonczay Z., Brimijoin S. Biochemistry and pathophysiology of the molecular forms of cholinesterases. Subcell Biochem. 1988;12:335–378. doi: 10.1007/978-1-4899-1681-5_10. [DOI] [PubMed] [Google Scholar]
  21. Raveh L., Ashani Y., Levy D., De La Hoz D., Wolfe A. D., Doctor B. P. Acetylcholinesterase prophylaxis against organophosphate poisoning. Quantitative correlation between protection and blood-enzyme level in mice. Biochem Pharmacol. 1989 Feb 1;38(3):529–534. doi: 10.1016/0006-2952(89)90394-8. [DOI] [PubMed] [Google Scholar]
  22. Razon N., Soreq H., Roth E., Bartal A., Silman I. Characterization of activities and forms of cholinesterases in human primary brain tumors. Exp Neurol. 1984 Jun;84(3):681–695. doi: 10.1016/0014-4886(84)90215-2. [DOI] [PubMed] [Google Scholar]
  23. Schimke R. T. Gene amplification in cultured animal cells. Cell. 1984 Jul;37(3):705–713. doi: 10.1016/0092-8674(84)90406-9. [DOI] [PubMed] [Google Scholar]
  24. Scotto K. W., Biedler J. L., Melera P. W. Amplification and expression of genes associated with multidrug resistance in mammalian cells. Science. 1986 May 9;232(4751):751–755. doi: 10.1126/science.2421411. [DOI] [PubMed] [Google Scholar]
  25. Seidman S., Soreq H. Coinjection of Xenopus oocytes with cDNA-produced and native mRNAs: a molecular biological approach to the tissue-specific processing of human cholinesterases. Int Rev Neurobiol. 1990;32:107–139. doi: 10.1016/s0074-7742(08)60581-4. [DOI] [PubMed] [Google Scholar]
  26. Slamon D. J., Clark G. M., Wong S. G., Levin W. J., Ullrich A., McGuire W. L. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987 Jan 9;235(4785):177–182. doi: 10.1126/science.3798106. [DOI] [PubMed] [Google Scholar]
  27. Slotman B. J., Rao B. R. Ovarian cancer (review). Etiology, diagnosis, prognosis, surgery, radiotherapy, chemotherapy and endocrine therapy. Anticancer Res. 1988 May-Jun;8(3):417–434. [PubMed] [Google Scholar]
  28. Soreq H., Gnatt A. Molecular biological search for human genes encoding cholinesterases. Mol Neurobiol. 1987 Spring-Summer;1(1-2):47–80. doi: 10.1007/BF02935264. [DOI] [PubMed] [Google Scholar]
  29. Soreq H., Malinger G., Zakut H. Expression of cholinesterase genes in human oocytes revealed by in-situ hybridization. Hum Reprod. 1987 Nov;2(8):689–693. doi: 10.1093/oxfordjournals.humrep.a136615. [DOI] [PubMed] [Google Scholar]
  30. Soreq H., Seidman S., Dreyfus P. A., Zevin-Sonkin D., Zakut H. Expression and tissue-specific assembly of human butyrylcholine esterase in microinjected Xenopus laevis oocytes. J Biol Chem. 1989 Jun 25;264(18):10608–10613. [PubMed] [Google Scholar]
  31. Soreq H., Zamir R., Zevin-Sonkin D., Zakut H. Human cholinesterase genes localized by hybridization to chromosomes 3 and 16. Hum Genet. 1987 Dec;77(4):325–328. doi: 10.1007/BF00291419. [DOI] [PubMed] [Google Scholar]
  32. Soreq H., Zevin-Sonkin D., Razon N. Expression of cholinesterase gene(s) in human brain tissues: translational evidence for multiple mRNA species. EMBO J. 1984 Jun;3(6):1371–1375. doi: 10.1002/j.1460-2075.1984.tb01979.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Spradling A. Gene amplification in dipteran chromosomes. Results Probl Cell Differ. 1987;14:199–212. doi: 10.1007/978-3-540-47783-9_12. [DOI] [PubMed] [Google Scholar]
  34. Yoshida M. C., Wada M., Satoh H., Yoshida T., Sakamoto H., Miyagawa K., Yokota J., Koda T., Kakinuma M., Sugimura T. Human HST1 (HSTF1) gene maps to chromosome band 11q13 and coamplifies with the INT2 gene in human cancer. Proc Natl Acad Sci U S A. 1988 Jul;85(13):4861–4864. doi: 10.1073/pnas.85.13.4861. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Zakut H., Even L., Birkenfeld S., Malinger G., Zisling R., Soreq H. Modified properties of serum cholinesterases in primary carcinomas. Cancer. 1988 Feb 15;61(4):727–737. doi: 10.1002/1097-0142(19880215)61:4<727::aid-cncr2820610416>3.0.co;2-l. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES