Skip to main content
British Journal of Cancer logoLink to British Journal of Cancer
. 1999 Feb;79(3-4):595–603. doi: 10.1038/sj.bjc.6690094

Differential expression of Hsp27 in normal oesophagus, Barrett's metaplasia and oesophageal adenocarcinomas

O S Soldes 1, R D Kuick 2, I A Thompson II 1, S J Hughes 1, M B Orringer 1, M D Iannettoni 1, S M Hanash 2, D G Beer 1
PMCID: PMC2362445  PMID: 10027336

Abstract

The protein expression patterns of normal, metaplastic and malignant oesophageal tissues were analysed by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) to identify changes associated with Barrett's metaplasia and transformation to oesophageal adenocarcinoma. Heat-shock protein 27 (Hsp27), a small heat-shock protein which is protective against cytotoxic stresses, was abundant in normal oesophagus. However, Hsp27 expression was markedly lower in Barrett's metaplasia and oesophageal adenocarcinomas. This was confirmed by immunohistochemical analysis. Hsp27 protein was most highly expressed in the upper layers of squamous epithelium and exhibited a pattern of expression that corresponded with the degree of squamous maturation. Northern and Southern analysis demonstrated Hsp27 to be regulated at the level of mRNA transcription or abundance. Normal oesophageal tissues were examined for gender differences in Hsp27 expression. Women expressed fourfold higher levels of Hsp27 mRNA, however, this difference was not appreciable in protein expression. Hsp27 protein was inducible by heat shock in Barrett's adenocarcinoma cell lines and an immortalized oesophageal epithelial cell line (HET-1A), but not by oestradiol. These results demonstrate abundant constitutive expression of the stress-response protein Hsp27 in the normal oesophagus, and suggest that low-level expression in Barrett's metaplasia may be one factor which may influence susceptibility to oesophageal adenocarcinoma development. © 1999 Cancer Research Campaign

Keywords: heat shock protein 27, Barrett's metaplasia, oesophagus, cancer, adenocarcinoma

Full Text

The Full Text of this article is available as a PDF (384.2 KB).

Selected References

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

  1. BARRETT N. R. Chronic peptic ulcer of the oesophagus and 'oesophagitis'. Br J Surg. 1950 Oct;38(150):175–182. doi: 10.1002/bjs.18003815005. [DOI] [PubMed] [Google Scholar]
  2. BARRETT N. R. The lower esophagus lined by columnar epithelium. Surgery. 1957 Jun;41(6):881–894. [PubMed] [Google Scholar]
  3. Blot W. J., Devesa S. S., Kneller R. W., Fraumeni J. F., Jr Rising incidence of adenocarcinoma of the esophagus and gastric cardia. JAMA. 1991 Mar 13;265(10):1287–1289. [PubMed] [Google Scholar]
  4. Bremner C. G., Lynch V. P., Ellis F. H., Jr Barrett's esophagus: congenital or acquired? An experimental study of esophageal mucosal regeneration in the dog. Surgery. 1970 Jul;68(1):209–216. [PubMed] [Google Scholar]
  5. Cameron A. J., Ott B. J., Payne W. S. The incidence of adenocarcinoma in columnar-lined (Barrett's) esophagus. N Engl J Med. 1985 Oct 3;313(14):857–859. doi: 10.1056/NEJM198510033131404. [DOI] [PubMed] [Google Scholar]
  6. Ciocca D. R., Adams D. J., Edwards D. P., Bjercke R. J., McGuire W. L. Distribution of an estrogen-induced protein with a molecular weight of 24,000 in normal and malignant human tissues and cells. Cancer Res. 1983 Mar;43(3):1204–1210. [PubMed] [Google Scholar]
  7. Dressler L. G., Ramzy I., Sledge G. W., McGuire W. L. A new marker of maturation in the cervix: the estrogen-regulated 24K protein. Obstet Gynecol. 1986 Dec;68(6):825–831. [PubMed] [Google Scholar]
  8. Dunn D. K., Whelan R. D., Hill B., King R. J. Relationship of HSP27 and oestrogen receptor in hormone sensitive and insensitive cell lines. J Steroid Biochem Mol Biol. 1993 Oct;46(4):469–479. doi: 10.1016/0960-0760(93)90101-2. [DOI] [PubMed] [Google Scholar]
  9. Edwards D. P., Adams D. J., Savage N., McGuire W. L. Estrogen induced synthesis of specific proteins in human breast cancer cells. Biochem Biophys Res Commun. 1980 Apr 14;93(3):804–812. doi: 10.1016/0006-291x(80)91148-1. [DOI] [PubMed] [Google Scholar]
  10. Fiers W. Tumor necrosis factor. Characterization at the molecular, cellular and in vivo level. FEBS Lett. 1991 Jul 22;285(2):199–212. doi: 10.1016/0014-5793(91)80803-b. [DOI] [PubMed] [Google Scholar]
  11. Fuqua S. A., Blum-Salingaros M., McGuire W. L. Induction of the estrogen-regulated "24K" protein by heat shock. Cancer Res. 1989 Aug 1;49(15):4126–4129. [PubMed] [Google Scholar]
  12. GOLDMAN M. C., BECKMAN R. C. Barrett syndrome. Case report with discussion about concepts of pathogenesis. Gastroenterology. 1960 Jul;39:104–110. [PubMed] [Google Scholar]
  13. Hanash S. M., Baier L. J., McCurry L., Schwartz S. A. Lineage-related polypeptide markers in acute lymphoblastic leukemia detected by two-dimensional gel electrophoresis. Proc Natl Acad Sci U S A. 1986 Feb;83(3):807–811. doi: 10.1073/pnas.83.3.807. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hanash S. M., Kuick R., Nichols D., Stoolman L. Quantitative analysis of a new marker for common acute lymphoblastic leukemia detected by two-dimensional electrophoresis. Dis Markers. 1988 Oct-Dec;6(4):209–220. [PubMed] [Google Scholar]
  15. Hanson L. A., Nuzum E. O., Jones B. C., Malkinson A. M., Beer D. G. Expression of the glucocorticoid receptor and K-ras genes in urethan-induced mouse lung tumors and transformed cell lines. Exp Lung Res. 1991 Mar-Apr;17(2):371–387. doi: 10.3109/01902149109064425. [DOI] [PubMed] [Google Scholar]
  16. Hesketh P. J., Clapp R. W., Doos W. G., Spechler S. J. The increasing frequency of adenocarcinoma of the esophagus. Cancer. 1989 Jul 15;64(2):526–530. doi: 10.1002/1097-0142(19890715)64:2<526::aid-cncr2820640228>3.0.co;2-b. [DOI] [PubMed] [Google Scholar]
  17. Hickey E., Brandon S. E., Sadis S., Smale G., Weber L. A. Molecular cloning of sequences encoding the human heat-shock proteins and their expression during hyperthermia. Gene. 1986;43(1-2):147–154. doi: 10.1016/0378-1119(86)90018-1. [DOI] [PubMed] [Google Scholar]
  18. Hinder R. A., Stein H. J. Oxygen-derived free radicals. Arch Surg. 1991 Jan;126(1):104–105. doi: 10.1001/archsurg.1991.01410250112019. [DOI] [PubMed] [Google Scholar]
  19. Huot J., Houle F., Spitz D. R., Landry J. HSP27 phosphorylation-mediated resistance against actin fragmentation and cell death induced by oxidative stress. Cancer Res. 1996 Jan 15;56(2):273–279. [PubMed] [Google Scholar]
  20. Huot J., Roy G., Lambert H., Chrétien P., Landry J. Increased survival after treatments with anticancer agents of Chinese hamster cells expressing the human Mr 27,000 heat shock protein. Cancer Res. 1991 Oct 1;51(19):5245–5252. [PubMed] [Google Scholar]
  21. Landry J., Lambert H., Zhou M., Lavoie J. N., Hickey E., Weber L. A., Anderson C. W. Human HSP27 is phosphorylated at serines 78 and 82 by heat shock and mitogen-activated kinases that recognize the same amino acid motif as S6 kinase II. J Biol Chem. 1992 Jan 15;267(2):794–803. [PubMed] [Google Scholar]
  22. Lavoie J. N., Lambert H., Hickey E., Weber L. A., Landry J. Modulation of cellular thermoresistance and actin filament stability accompanies phosphorylation-induced changes in the oligomeric structure of heat shock protein 27. Mol Cell Biol. 1995 Jan;15(1):505–516. doi: 10.1128/mcb.15.1.505. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. McBride T. J., Preston B. D., Loeb L. A. Mutagenic spectrum resulting from DNA damage by oxygen radicals. Biochemistry. 1991 Jan 8;30(1):207–213. doi: 10.1021/bi00215a030. [DOI] [PubMed] [Google Scholar]
  24. Mehlen P., Kretz-Remy C., Préville X., Arrigo A. P. Human hsp27, Drosophila hsp27 and human alphaB-crystallin expression-mediated increase in glutathione is essential for the protective activity of these proteins against TNFalpha-induced cell death. EMBO J. 1996 Jun 3;15(11):2695–2706. [PMC free article] [PubMed] [Google Scholar]
  25. Mehlen P., Mehlen A., Guillet D., Preville X., Arrigo A. P. Tumor necrosis factor-alpha induces changes in the phosphorylation, cellular localization, and oligomerization of human hsp27, a stress protein that confers cellular resistance to this cytokine. J Cell Biochem. 1995 Jun;58(2):248–259. doi: 10.1002/jcb.240580213. [DOI] [PubMed] [Google Scholar]
  26. Mehlen P., Preville X., Chareyron P., Briolay J., Klemenz R., Arrigo A. P. Constitutive expression of human hsp27, Drosophila hsp27, or human alpha B-crystallin confers resistance to TNF- and oxidative stress-induced cytotoxicity in stably transfected murine L929 fibroblasts. J Immunol. 1995 Jan 1;154(1):363–374. [PubMed] [Google Scholar]
  27. Moscow J. A., Fairchild C. R., Madden M. J., Ransom D. T., Wieand H. S., O'Brien E. E., Poplack D. G., Cossman J., Myers C. E., Cowan K. H. Expression of anionic glutathione-S-transferase and P-glycoprotein genes in human tissues and tumors. Cancer Res. 1989 Mar 15;49(6):1422–1428. [PubMed] [Google Scholar]
  28. Naef A. P., Savary M., Ozzello L. Columnar-lined lower esophagus: an acquired lesion with malignant predisposition. Report on 140 cases of Barrett's esophagus with 12 adenocarcinomas. J Thorac Cardiovasc Surg. 1975 Nov;70(5):826–835. [PubMed] [Google Scholar]
  29. Olyaee M., Sontag S., Salman W., Schnell T., Mobarhan S., Eiznhamer D., Keshavarzian A. Mucosal reactive oxygen species production in oesophagitis and Barrett's oesophagus. Gut. 1995 Aug;37(2):168–173. doi: 10.1136/gut.37.2.168. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Reed P. I., Johnston B. J. The changing incidence of oesophageal cancer. Endoscopy. 1993 Nov;25(9):606–608. doi: 10.1055/s-2007-1010414. [DOI] [PubMed] [Google Scholar]
  31. Richards E. H., Hickey E., Weber L., Master J. R. Effect of overexpression of the small heat shock protein HSP27 on the heat and drug sensitivities of human testis tumor cells. Cancer Res. 1996 May 15;56(10):2446–2451. [PubMed] [Google Scholar]
  32. Skinner D. B., Walther B. C., Riddell R. H., Schmidt H., Iascone C., DeMeester T. R. Barrett's esophagus. Comparison of benign and malignant cases. Ann Surg. 1983 Oct;198(4):554–565. doi: 10.1097/00000658-198310000-00016. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Spechler S. J., Robbins A. H., Rubins H. B., Vincent M. E., Heeren T., Doos W. G., Colton T., Schimmel E. M. Adenocarcinoma and Barrett's esophagus. An overrated risk? Gastroenterology. 1984 Oct;87(4):927–933. [PubMed] [Google Scholar]
  34. Stoner G. D., Kaighn M. E., Reddel R. R., Resau J. H., Bowman D., Naito Z., Matsukura N., You M., Galati A. J., Harris C. C. Establishment and characterization of SV40 T-antigen immortalized human esophageal epithelial cells. Cancer Res. 1991 Jan 1;51(1):365–371. [PubMed] [Google Scholar]
  35. Strahler J. R., Kuick R., Eckerskorn C., Lottspeich F., Richardson B. C., Fox D. A., Stoolman L. M., Hanson C. A., Nichols D., Tueche H. J. Identification of two related markers for common acute lymphoblastic leukemia as heat shock proteins. J Clin Invest. 1990 Jan;85(1):200–207. doi: 10.1172/JCI114413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Trautinger F., Kindas-Mügge I., Dekrout B., Knobler R. M., Metze D. Expression of the 27-kDa heat shock protein in human epidermis and in epidermal neoplasms: an immunohistological study. Br J Dermatol. 1995 Aug;133(2):194–202. doi: 10.1111/j.1365-2133.1995.tb02615.x. [DOI] [PubMed] [Google Scholar]
  37. Trush M. A., Kensler T. W. An overview of the relationship between oxidative stress and chemical carcinogenesis. Free Radic Biol Med. 1991;10(3-4):201–209. doi: 10.1016/0891-5849(91)90077-g. [DOI] [PubMed] [Google Scholar]
  38. Welch W. J. Phorbol ester, calcium ionophore, or serum added to quiescent rat embryo fibroblast cells all result in the elevated phosphorylation of two 28,000-dalton mammalian stress proteins. J Biol Chem. 1985 Mar 10;260(5):3058–3062. [PubMed] [Google Scholar]
  39. Wetscher G. J., Hinder P. R., Bagchi D., Perdikis G., Redmond E. J., Glaser K., Adrian T. E., Hinder R. A. Free radical scavengers prevent reflux esophagitis in rats. Dig Dis Sci. 1995 Jun;40(6):1292–1296. doi: 10.1007/BF02065541. [DOI] [PubMed] [Google Scholar]
  40. Wetscher G. J., Hinder R. A., Bagchi D., Hinder P. R., Bagchi M., Perdikis G., McGinn T. Reflux esophagitis in humans is mediated by oxygen-derived free radicals. Am J Surg. 1995 Dec;170(6):552–557. doi: 10.1016/s0002-9610(99)80014-2. [DOI] [PubMed] [Google Scholar]
  41. Wetscher G. J., Perdikis G., Kretchmar D. H., Stinson R. G., Bagchi D., Redmond E. J., Adrian T. E., Hinder R. A. Esophagitis in Sprague-Dawley rats is mediated by free radicals. Dig Dis Sci. 1995 Jun;40(6):1297–1305. doi: 10.1007/BF02065542. [DOI] [PubMed] [Google Scholar]
  42. Winters C., Jr, Spurling T. J., Chobanian S. J., Curtis D. J., Esposito R. L., Hacker J. F., 3rd, Johnson D. A., Cruess D. F., Cotelingam J. D., Gurney M. S. Barrett's esophagus. A prevalent, occult complication of gastroesophageal reflux disease. Gastroenterology. 1987 Jan;92(1):118–124. [PubMed] [Google Scholar]
  43. Wu W., Welsh M. J. Expression of the 25-kDa heat-shock protein (HSP27) correlates with resistance to the toxicity of cadmium chloride, mercuric chloride, cis-platinum(II)-diammine dichloride, or sodium arsenite in mouse embryonic stem cells transfected with sense or antisense HSP27 cDNA. Toxicol Appl Pharmacol. 1996 Nov;141(1):330–339. doi: 10.1006/taap.1996.0290. [DOI] [PubMed] [Google Scholar]

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

RESOURCES