Skip to main content
PMC home page
Annals of Surgery logoLink to Annals of Surgery
. 1994 Oct;220(4):484–491. doi: 10.1097/00000658-199410000-00007

Expression of the neurotensin gene in fetal human liver and fibrolamellar carcinoma.

J A Ehrenfried 1, Z Zhou 1, J C Thompson 1, B M Evers 1
PMCID: PMC1234420  PMID: 7944660

Abstract

OBJECTIVE: This study determined whether the neurotensin gene (NT/N) is expressed in the normal adult liver and focal nodular hyperplasia (FNH) and confirmed NT/N expression in fibrolamellar carcinoma; whether NT/N or the neurotensin receptor is expressed in the fetal liver; and whether hepatic resection leads to expression of NT/N. SUMMARY BACKGROUND DATA: Neurotensin (NT), a gut tridecapeptide localized in the gastrointestinal tract of the adult to the small bowel, is an important hormone-regulating gut motility, secretion, and mucosal growth. Expression of the NT/N gene has been identified in fibrolamellar carcinomas, but NT/N is not known to be expressed in the normal liver. METHODS: Sensitive ribonuclease (RNase) protection assays were used to determine whether NT/N is expressed in fibrolamellar carcinoma, FNH, or healthy fetal and adult livers. The authors also determined whether the receptor for NT was present in the fetal liver and whether liver resection and subsequent regeneration could lead to re-expression of NT/N in the rat. RESULTS: Neurotensin is expressed in fibrolamellar carcinoma and in the fetal human liver, but not in the adult liver or the samples of FNH. In addition, the authors were not able to detect expression of the NT receptor in the fetal liver and did not identify NT/N gene activation in the regenerating liver of the rat. CONCLUSIONS: The NT/N gene will be a useful molecular marker to differentiate fibrolamellar carcinoma from other liver tumors. The finding of NT/N expression in the fetal liver suggests a stem cell descendant that is common to both the liver and gut. The absence of NT/N expression in the regenerating liver suggests that NT does not play a role in this rapid growth process.

Full text

PDF
489

Images in this article

486Figure 1.
on p.486
487Figure 2.
on p.487
487Figure 3.
on p.487
487Figure 4.
on p.487

Selected References

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

  1. Andersson S., Rosell S., Hjelmquist U., Chang D., Folkers K. Inhibition of gastric and intestinal motor activity in dogs by (Gln4) neurotensin. Acta Physiol Scand. 1977 Jun;100(2):231–235. doi: 10.1111/j.1748-1716.1977.tb05941.x. [DOI] [PubMed] [Google Scholar]
  2. Armstrong M. J., Parker M. C., Ferris C. F., Leeman S. E. Neurotensin stimulates [3H]oleic acid translocation across rat small intestine. Am J Physiol. 1986 Dec;251(6 Pt 1):G823–G829. doi: 10.1152/ajpgi.1986.251.6.G823. [DOI] [PubMed] [Google Scholar]
  3. BUCHER N. L. REGENERATION OF MAMMALIAN LIVER. Int Rev Cytol. 1963;15:245–300. doi: 10.1016/s0074-7696(08)61119-5. [DOI] [PubMed] [Google Scholar]
  4. Baca I., Feurle G. E., Schwab A., Mittmann U., Knauf W., Lehnert T. Effect of neurotensin on exocrine pancreatic secretion in dogs. Digestion. 1982;23(3):174–183. doi: 10.1159/000198725. [DOI] [PubMed] [Google Scholar]
  5. Bean A. J., Dagerlind A., Hökfelt T., Dobner P. R. Cloning of human neurotensin/neuromedin N genomic sequences and expression in the ventral mesencephalon of schizophrenics and age/sex matched controls. Neuroscience. 1992 Sep;50(2):259–268. doi: 10.1016/0306-4522(92)90421-w. [DOI] [PubMed] [Google Scholar]
  6. Bedi D. G., Kumar R., Morettin L. B., Gourley K. Fibrolamellar carcinoma of the liver: CT, ultrasound and angiography. Case report. Eur J Radiol. 1988 May;8(2):109–112. [PubMed] [Google Scholar]
  7. Berman M. A., Burnham J. A., Sheahan D. G. Fibrolamellar carcinoma of the liver: an immunohistochemical study of nineteen cases and a review of the literature. Hum Pathol. 1988 Jul;19(7):784–794. doi: 10.1016/s0046-8177(88)80261-2. [DOI] [PubMed] [Google Scholar]
  8. Buamah P. K., McArdle P., Bennett M., James O. F., Lendrum R. A pleomorphic hepatocellular carcinoma with biochemical features of fibrolamellar hepatocellular carcinoma. J Surg Oncol. 1986 Jun;32(2):93–95. doi: 10.1002/jso.2930320210. [DOI] [PubMed] [Google Scholar]
  9. Carraway R., Leeman S. E. The isolation of a new hypotensive peptide, neurotensin, from bovine hypothalami. J Biol Chem. 1973 Oct 10;248(19):6854–6861. [PubMed] [Google Scholar]
  10. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  11. Chung D. H., Evers B. M., Shimoda I., Townsend C. M., Jr, Rajaraman S., Thompson J. C. Effect of neurotensin on gut mucosal growth in rats with jejunal and ileal Thiry-Vella fistulas. Gastroenterology. 1992 Oct;103(4):1254–1259. doi: 10.1016/0016-5085(92)91512-3. [DOI] [PubMed] [Google Scholar]
  12. Collier N. A., Weinbren K., Bloom S. R., Lee Y. C., Hodgson H. J., Blumgart L. H. Neurotensin secretion by fibrolamellar carcinoma of the liver. Lancet. 1984 Mar 10;1(8376):538–540. doi: 10.1016/s0140-6736(84)90934-6. [DOI] [PubMed] [Google Scholar]
  13. Darnell J. E., Jr Variety in the level of gene control in eukaryotic cells. Nature. 1982 Jun 3;297(5865):365–371. doi: 10.1038/297365a0. [DOI] [PubMed] [Google Scholar]
  14. Evers B. M., Bold R. J., Ehrenfried J. A., Li J., Townsend C. M., Jr, Klimpel G. R. Characterization of functional neurotensin receptors on human lymphocytes. Surgery. 1994 Aug;116(2):134–140. [PubMed] [Google Scholar]
  15. Evers B. M., Ishizuka J., Chung D. H., Townsend C. M., Jr, Thompson J. C. Neurotensin expression and release in human colon cancers. Ann Surg. 1992 Oct;216(4):423–431. doi: 10.1097/00000658-199210000-00005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Evers B. M., Ishizuka J., Townsend C. M., Jr, Rajaraman S., Thompson J. C. Expression of neurotensin messenger RNA in a human carcinoid tumor. Ann Surg. 1991 Oct;214(4):448–455. doi: 10.1097/00000658-199110000-00009. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Evers B. M., Izukura M., Chung D. H., Parekh D., Yoshinaga K., Greeley G. H., Jr, Uchida T., Townsend C. M., Jr, Thompson J. C. Neurotensin stimulates growth of colonic mucosa in young and aged rats. Gastroenterology. 1992 Jul;103(1):86–91. doi: 10.1016/0016-5085(92)91099-p. [DOI] [PubMed] [Google Scholar]
  18. Evers B. M., Izukura M., Townsend C. M., Jr, Uchida T., Thompson J. C. Neurotensin prevents intestinal mucosal hypoplasia in rats fed an elemental diet. Dig Dis Sci. 1992 Mar;37(3):426–431. doi: 10.1007/BF01307738. [DOI] [PubMed] [Google Scholar]
  19. Evers B. M., Rajaraman S., Chung D. H., Townsend C. M., Jr, Wang X., Graves K., Thompson J. C. Developmental expression of the neurotensin gene in the rat liver. Ann Surg. 1993 Aug;218(2):183–188. doi: 10.1097/00000658-199308000-00010. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Evers B. M., Rajaraman S., Chung D. H., Townsend C. M., Jr, Wang X., Graves K., Thompson J. C. Differential expression of the neurotensin gene in the developing rat and human gastrointestinal tract. Am J Physiol. 1993 Sep;265(3 Pt 1):G482–G490. doi: 10.1152/ajpgi.1993.265.3.G482. [DOI] [PubMed] [Google Scholar]
  21. Hasegawa K., Carr B. I. Neurotensin-amplification of DNA synthesis stimulated by EGF or TGF alpha in primary cultures of adult rat hepatocytes. Cell Struct Funct. 1993 Apr;18(2):105–110. doi: 10.1247/csf.18.105. [DOI] [PubMed] [Google Scholar]
  22. Hasegawa K., Kar S., Carr B. I. Stimulation of hepatocyte DNA synthesis by neurotensin. J Cell Physiol. 1994 Feb;158(2):215–222. doi: 10.1002/jcp.1041580202. [DOI] [PubMed] [Google Scholar]
  23. Kapuscinski M., Shulkes A., Read D., Hardy K. J. Expression of neurotensin in endocrine tumors. J Clin Endocrinol Metab. 1990 Jan;70(1):100–106. doi: 10.1210/jcem-70-1-100. [DOI] [PubMed] [Google Scholar]
  24. Kingston J. E., Herbert A., Draper G. J., Mann J. R. Association between hepatoblastoma and polyposis coli. Arch Dis Child. 1983 Dec;58(12):959–962. doi: 10.1136/adc.58.12.959. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Krush A. J., Traboulsi E. I., Offerhaus J. A., Maumenee I. H., Yardley J. H., Levin L. S. Hepatoblastoma, pigmented ocular fundus lesions and jaw lesions in Gardner syndrome. Am J Med Genet. 1988 Feb;29(2):323–332. doi: 10.1002/ajmg.1320290211. [DOI] [PubMed] [Google Scholar]
  26. Lee Y. C., Bacarese-Hamilton A. J., Wood S. M., Blumgart L. H., Bloom S. R. Chromatographic characterisation of neurotensin-like immunoreactivity in plasma and tissue extracts from hepatoma patients. Clin Chim Acta. 1985 Jun 30;149(1):29–36. doi: 10.1016/0009-8981(85)90270-0. [DOI] [PubMed] [Google Scholar]
  27. Michalopoulos G. K. Liver regeneration: molecular mechanisms of growth control. FASEB J. 1990 Feb 1;4(2):176–187. [PubMed] [Google Scholar]
  28. Mitchell P. J., Tjian R. Transcriptional regulation in mammalian cells by sequence-specific DNA binding proteins. Science. 1989 Jul 28;245(4916):371–378. doi: 10.1126/science.2667136. [DOI] [PubMed] [Google Scholar]
  29. Read D., Shulkes A., Fernley R., Simpson R. Characterization of neurotensin(6-13) from an hepatic fibrolamellar carcinoma. Peptides. 1991 Jul-Aug;12(4):887–892. doi: 10.1016/0196-9781(91)90152-f. [DOI] [PubMed] [Google Scholar]
  30. Reinecke M. Neurotensin. Immunohistochemical localization in central and peripheral nervous system and in endocrine cells and its functional role as neurotransmitter and endocrine hormone. Prog Histochem Cytochem. 1985;16(1):1–172. [PubMed] [Google Scholar]
  31. Shortell C. K., Schwartz S. I. Hepatic adenoma and focal nodular hyperplasia. Surg Gynecol Obstet. 1991 Nov;173(5):426–431. [PubMed] [Google Scholar]
  32. Soreide O., Czerniak A., Bradpiece H., Bloom S., Blumgart L. Characteristics of fibrolamellar hepatocellular carcinoma. A study of nine cases and a review of the literature. Am J Surg. 1986 Apr;151(4):518–523. doi: 10.1016/0002-9610(86)90117-0. [DOI] [PubMed] [Google Scholar]
  33. Tatematsu M., Kaku T., Medline A., Farber E. Intestinal metaplasia as a common option of oval cells in relation to cholangiofibrosis in liver of rats exposed to 2-acetylaminofluorene. Lab Invest. 1985 Apr;52(4):354–362. [PubMed] [Google Scholar]
  34. Vita N., Laurent P., Lefort S., Chalon P., Dumont X., Kaghad M., Gully D., Le Fur G., Ferrara P., Caput D. Cloning and expression of a complementary DNA encoding a high affinity human neurotensin receptor. FEBS Lett. 1993 Feb 8;317(1-2):139–142. doi: 10.1016/0014-5793(93)81509-x. [DOI] [PubMed] [Google Scholar]
  35. Wood J. G., Hoang H. D., Bussjaeger L. J., Solomon T. E. Neurotensin stimulates growth of small intestine in rats. Am J Physiol. 1988 Dec;255(6 Pt 1):G813–G817. doi: 10.1152/ajpgi.1988.255.6.G813. [DOI] [PubMed] [Google Scholar]
  36. Yoshida Y., Kaneko A., Chisaka N., Onoé T. Appearance of intestinal type of tumor cells in hepatoma tissue induced by 3'-methyl-4-dimethylaminoazobenzene. Cancer Res. 1978 Sep;38(9):2753–2758. [PubMed] [Google Scholar]

Articles from Annals of Surgery are provided here courtesy of Lippincott, Williams, and Wilkins

RESOURCES