Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Advertisement

British Journal of Cancer
  • View all journals
  • Search
  • My Account Login
  • Content Explore content
  • About the journal
  • Publish with us
  • Sign up for alerts
  • RSS feed
  1. nature
  2. british journal of cancer
  3. regular article
  4. article
Differential expression of Hsp27 in normal oesophagus, Barrett’s metaplasia and oesophageal adenocarcinomas
Download PDF
Download PDF
  • Regular Article
  • Open access
  • Published: 14 January 1999

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

  • O S Soldes1,
  • R D Kuick2,
  • I A Thompson II1,
  • S J Hughes1,
  • M B Orringer1,
  • M D Iannettoni1,
  • S M Hanash2 &
  • …
  • D G Beer1 

British Journal of Cancer volume 79, pages 595–603 (1999)Cite this article

  • 923 Accesses

  • 98 Citations

  • Metrics details

This article has been updated

Summary

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.

Similar content being viewed by others

On-chip Raman spectroscopy of live single cells for the staging of oesophageal adenocarcinoma progression

Article Open access 19 January 2024

Profile of esophageal squamous cell carcinoma mutations in Brazilian patients

Article Open access 18 October 2021

Sex differences in esophageal cancer overall and by histological subtype

Article Open access 28 March 2022

Article PDF

Change history

  • 16 November 2011

    This paper was modified 12 months after initial publication to switch to Creative Commons licence terms, as noted at publication

References

  • Al-Kasspooles, M., Moore, J. H., Orringer, M. B. & Beer, D. G. (1993). Amplification and overexpression of the EGFR and erbB-2 genes in human esophageal adenocarcinomas. Int J Cancer 54: 213–219.

    Article  CAS  Google Scholar 

  • Ames, B. N., Shigenaga, M. K. & Hagen, T. M. (1993). Oxidants, antioxidants, and the degenerative diseases of aging. Proc Natl Acad Sci, USA 90: 7915–7922.

    Article  CAS  Google Scholar 

  • Arrigo, A-P & Welch, W. J. (1987). Characterization and purification of the small 28,000-Dalton mammalian heat shock protein. J Biol Chem 262: 15359–15369.

    CAS  PubMed  Google Scholar 

  • Barrett, N. R. (1950). Chronic peptic ulcer of the oesophagus and ‘oesophagitis’. Br J Surg 38: 175–182.

    Article  CAS  Google Scholar 

  • Barrett, N. R. (1957). The lower esophagus lined by columnar epithelium. Surgery 41: 881–894.

    CAS  PubMed  Google Scholar 

  • Blot, W. J., Devesa, S. S., Kneller, R. W. & Fraumeni, J. F. (1991). Rising incidence of adenocarcinoma of the esophagus and gastric cardia. JAMA 265: 1287–1289.

    Article  CAS  Google Scholar 

  • Bremner, C. G., Lynch, V. P. & Ellis, F. H. (1970). Barrett’s esophagus: congenital or acquired? An experimental study of esophageal mucosal regeneration in the dog. Surgery 68: 209–216.

    CAS  PubMed  Google Scholar 

  • Cameron, A. J., Ott, B. J. & Payne, W. S. (1985). The incidence of adenocarcinoma in columnar-lined (Barrett’s) esophagus. N Engl J Med 313: 857–859.

    Article  CAS  Google Scholar 

  • Ciocca, R. D., Adams, D. J., Edwards, D. P., Bjercke, R. J. & McGuire, W. L. (1983). Distribution of an estrogen-induced protein with a molecular weight of 24,000 in normal and malignant human tissues and cells. Cancer Res 43: 1204–1210.

    CAS  PubMed  Google Scholar 

  • Dressler, L. G., Ramzy, I., Sledge, G. W. & McGuire, W. L. (1986). A new marker of maturation in the cervix: the estrogen-regulated 24k protein. Obstet Gynecol 68: 825–831.

    CAS  PubMed  Google Scholar 

  • Dunn, D. K., Whelan, R. D. H., Hill, B. & King, R. J. B. (1993). Relationship of HSP27 and oestrogen receptor in hormone sensitive and insensitive cell lines. J Steroid Biochem Mol Biol 46: 469–479.

    Article  CAS  Google Scholar 

  • Edwards, D. P., Adams, D. J., Savage, N. & McGuire, W. L. (1980). Estrogen induced synthesis of specific proteins in human breast cancer cells. Biochem Biophys Res Commun 93: 804–812.

    Article  CAS  Google Scholar 

  • Fiers, W. (1991). Tumor necrosis factor: characterization at the molecular, cellular and in vivo level. FEBS Lett 285: 199–212.

    Article  CAS  Google Scholar 

  • Fuqua, S. A. W., Blum-Salingaros, M. & McGuire, W. L. (1989). Induction of the estrogen-regulated ‘24K’ protein by heat shock. Cancer Res 49: 4126–4129.

    CAS  PubMed  Google Scholar 

  • Goldman, M. C. & Beckman, R. C. (1960). Barrett syndrome: case report with discussion about concepts of pathogenesis. Gastroenterology 39: 104–110.

    CAS  PubMed  Google Scholar 

  • Hamilton, S. R. (1992). Oesophagitis. In Pathology of the Gastrointestinal Tract, Ming S-C and Goldman H (eds), pp. 381–438, WB Saunders: Philadelphia

    Google Scholar 

  • Hanash, S. M., Baier, L. J., McCurry, L. & Schwartz, S. A. (1986). Lineage-related polypeptide markers in acute lymphoblastic leukemia detected by two-dimensional gel electrophoresis. Proc Natl Acad Sci USA 83: 807–811.

    Article  CAS  Google Scholar 

  • Hanash, S. M., Kuick, R., Nichols, D. & Stoolman, L. (1988). Quantitative analysis of a new marker for common acute lymphoblastic leukemia detected by two-dimensional electrophoresis. Dis Markers 6: 209–220.

    CAS  PubMed  Google Scholar 

  • Hanson, L. A., Nuzum, E. O., Jones, B. C., Malkinson, A. M. & Beer, D. G. (1991). Expression of the glucocorticoid receptor and K-ras genes in urethan-induced mouse lung tumors and transformed cell lines. Exp Lung Res 17: 371–387.

    Article  CAS  Google Scholar 

  • Hesketh, P. J., Clapp, R. W., Doos, W. G. & Spechler, S. J. (1989). The increasing frequency of adenocarcinoma of the esophagus. Cancer 64: 526–530.

    Article  CAS  Google Scholar 

  • Hickey, E., Brandon, S. E., Sadis, S., Smale, G. & Weber, L. A. (1986). Molecular cloning of sequences encoding the human heat-shock proteins and their expression during hyperthermia. Gene 43: 147–154.

    Article  CAS  Google Scholar 

  • Hinder, R. A. & Stein, H. J. (1991). Oxygen-derived free radicals. Arch Surg 126: 104–105.

    Article  CAS  Google Scholar 

  • Hout, J., Roy, G., Lambert, H., Chretien, P. & Landry, J. (1991). Increased survival after treatments with anticancer agents of Chinese hamster cells expressing the human Mr 27,000 heat shock protein. Cancer Res 51: 5245–5252.

    Google Scholar 

  • Hout, J., Houle, F., Spitz, D. R. & Landry, J. (1996). Hsp27 phosphorylation-mediated resistance against actin fragmentation and cell death induced by oxidative stress. Cancer Res 56: 273–279.

    Google Scholar 

  • Kuick, R. D., Hanash, S. M., Chu, E. H. Y. & Strahler, J. R. (1987). A comparison of some adjustment techniques for use with quantitative spot data from two-dimensional gels. Electrophoresis 8: 199–204.

    Article  CAS  Google Scholar 

  • Landry, J., Chretien, P., Lambert, H., Hickey, E. & Weber, L. A. (1989). Heat shock resistance conferred by expression of the human hsp27 gene in rodent cells. J Cell Biol 109: 7–15.

    Article  CAS  Google Scholar 

  • Landry, J., Chretien, P., Laszlo, A. & Lambert, H. (1991). Phosphorylation of Hsp27 during development and decay of thermotolerance in Chinese hamster cells. J Cell Physiol 147: 93–101.

    Article  CAS  Google Scholar 

  • Landry, J., Lambert, H., Zhou, M., Lavoie, J. N., Hickey, E., Weber, L. A. & Anderson, C. W. (1992). 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 267: 794–803.

    CAS  PubMed  Google Scholar 

  • Lavoie, J. N., Lambert, H., Hickey, E., Weber, L. A. & Landry, J. (1995). Modulation of cellular thermoresistance and actin filament stability accompanies phosphorylation-induced changes in the oligomeric structure of heat shock protein 27. Mol Cell Biol 15: 505–516.

    Article  CAS  Google Scholar 

  • McBride, T. J., Preston, B. D. & Loeb, L. A. (1991). Mutagenic spectrum resulting from DNA damage by oxygen radicals. Biochemistry 30: 207–213.

    Article  CAS  Google Scholar 

  • Mehlen, P., Mehlen, A., Guillet, D., Preville, X. & Arrigo, A-P (1995a). Tumor necrosis factor-α 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 58: 248–259.

    Article  CAS  Google Scholar 

  • Mehlen, P., Preville, X., Chareyron, P., Briolay, J., Klemenz, R. & Arrigo, A-P (1995b). Constitutive expression of human hsp27, Drosophila hsp27, or human aB-crystallin confers resistance to TNF- and oxidative stress-induced cytotoxicity in stably transfected murine L929 fibroblasts. J Immunol 154: 363–374.

    CAS  PubMed  Google Scholar 

  • Mehlen, P., Kretz-Remy, C., Preville, X. & Arrigo, A-P (1996). Human hsp27, Drosophila hsp27 and human αB-crystallin expression-mediated increase in glutathione is essential for the protective activity of these proteins against TNFα-induced cell death. EMBO J 15: 2695–2706.

    Article  CAS  Google Scholar 

  • 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. (1989). Expression of anionic glutathione-S-transferase and p-glycoprotein genes in human tissues and tumors. Cancer Res 49: 1422–1428.

    CAS  PubMed  Google Scholar 

  • Naef, A. P., Savary, M. & Ozzello, L. (1975). Columnar-lined lower esophagus: an acquired lesion with malignant predisposition. J Thorac Cardiovasc Surg 70: 826–835.

    CAS  PubMed  Google Scholar 

  • Olyaee, M., Sontag, S., Salman, W., Schnell, T., Mobarhan, S., Eiznhamer, D. & Keshavarzian, A. (1995). Mucosal reactive oxygen species production in oesophagitis and Barrett’s oesophagus. Gut 37: 168–173.

    Article  CAS  Google Scholar 

  • Rachwal, W. J., Bongiorno, P. F., Orringer, M. B., Whyte, R. I., Ethier, S. P. & Beer, D. G. (1995). Expression and activation of erbB-2 and epidermal growth factor receptor in lung adenocarcinomas. Br J Cancer 72: 56–64.

    Article  CAS  Google Scholar 

  • Reed, P. I. & Johnson, B. J. (1993). The changing incidence of oesophageal cancer. Endoscopy 25: 606–608.

    Article  CAS  Google Scholar 

  • Richards, E. H., Hickey, E., Weber, L. & Masters, J. R. W. (1996). Effect of overexpression of the small heat shock protein HSP27 on the heat and drug sensitivities of human testis tumor cells. Cancer Res 56: 2446–2451.

    CAS  PubMed  Google Scholar 

  • Schnell, T., Sontag, S., Wanner, J., Chintam, R., Chejfec, G., O’Connell, S. & Moroni, B. (1985). Endoscopic screening for Barrett’s esophagus (BE), esophageal adenocarcinoma (AdCa) and other mucosal changes in ambulatory subjects with symptomatic gastroesophageal reflux (GER). Gastroenterology 88: 1576

    Google Scholar 

  • Skinner, D. B., Walther, B. C., Riddell, R. H., Schmidt, H., Iascone, C. & Demeester, T. R. (1983). Barrett’s esophagus. Comparison of benign and malignant cases. Ann Surg 198: 554–566.

    Article  CAS  Google Scholar 

  • Spechler, S. J., Robbins, A. H., Rubins, H. B., Vincent, M. E., Heeren, T., Doos, W. G., Colton, T. & Schimmel, E. M. (1984). Adenocarcinoma and Barrett’s esophagus: an overrated risk?. Gastroenterology 87: 927–933.

    CAS  PubMed  Google Scholar 

  • 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. (1991). Establishment and characterization of SV40 T-antigen immortalized human esophageal epithelia cells. Cancer Res 51: 365–371.

    CAS  PubMed  Google Scholar 

  • 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. & Hanash, S. M. (1990). Identification of two related markers for common acute lymphoblastic leukemia as heat shock proteins. J Clin Invest 85: 200–207.

    Article  CAS  Google Scholar 

  • Trautinger, F., Kindas-Mugge, I., Dekrout, B., Knobler, R. M. & Metze, D. (1995). Expression of the 27-kDa heat shock protein in human epidermis and in epidermal neoplasms: an immunohistological study. Br J Dermatol 133: 194–202.

    Article  CAS  Google Scholar 

  • Trush, M. A. & Kensler, T. W. (1991). An overview of the relationship between oxidative stress and chemical carcinogenesis. Free Radical Biol Med 10: 201–209.

    Article  CAS  Google Scholar 

  • Van Der Veen, A. H., Dees, J., Blankensteijn, J. D. & Van Blankenstein, M. (1989). Adenocarcinoma in Barrett’s oesophagus: an overrated risk. Gut 30: 14–18.

    Article  CAS  Google Scholar 

  • Welch, W. J. (1985). 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 260: 3058–3062.

    CAS  PubMed  Google Scholar 

  • Wetscher, G. J., Hinder, P. R., Bagchi, D., Perdikis, G., Redmond, E. J., Glaser, K., Adrian, T. E. & Hinder, R. A. (1995a). Free radical scavengers prevent reflux esophagitis in rats. Dig Dis Sci 40: 1292–1296.

    Article  CAS  Google Scholar 

  • Wetscher, G. J., Hinder, R. A., Bagchi, D., Hinder, P. R., Bagchi, M., Perdikis, G. & McGinn, T. (1995b). Reflux esophagitis in humans is mediated by oxygen-derived free radicals. Am J Surg 170: 552–557.

    Article  CAS  Google Scholar 

  • Wetscher, G. J., Perdikis, G., Kretchmar, D. H., Stinson, R. G., Bagchi, D., Redmond, E. J., Adrian, T. E. & Hinder, R. A. (1995c). Esophagitis in Sprague-Dawley rats is mediated by free radicals. Dig Dis Sci 40: 1297–1305.

    Article  CAS  Google Scholar 

  • Wheater, P. R., Burkitt, H. G. & Daniels, V. G. (1987). Functional Histology: a Text and Colour Atlas, pp. 64–78, Churchill Livingstone: New York

    Google Scholar 

  • Winters, C., Spurling, T. J., Chobanian, S. J., Curtis, D. J., Esposito, R. L., Hacker, J. F., Johnson, D. A., Cruess, D. F., Cotelingam, J. D., Gurney, M. S. & Cattau, E. L. (1987). Barrett’s esophagus: a prevalent, occult complication of gastroesophageal reflux disease. Gastroenterology 92: 118–124.

    Article  Google Scholar 

  • Wu, W. & Welsh, M. J. (1996). 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 141: 330–339.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Surgery, Thoracic Tumor Biology Laboratory, Section of Thoracic Surgery, University of Michigan Medical Center, Ann Arbor, 48109, MI, USA

    O S Soldes, I A Thompson II, S J Hughes, M B Orringer, M D Iannettoni & D G Beer

  2. Department of Pediatrics, University of Michigan Medical Center, Ann Arbor, 48109, MI, USA

    R D Kuick & S M Hanash

Authors
  1. O S Soldes
    View author publications

    Search author on:PubMed Google Scholar

  2. R D Kuick
    View author publications

    Search author on:PubMed Google Scholar

  3. I A Thompson II
    View author publications

    Search author on:PubMed Google Scholar

  4. S J Hughes
    View author publications

    Search author on:PubMed Google Scholar

  5. M B Orringer
    View author publications

    Search author on:PubMed Google Scholar

  6. M D Iannettoni
    View author publications

    Search author on:PubMed Google Scholar

  7. S M Hanash
    View author publications

    Search author on:PubMed Google Scholar

  8. D G Beer
    View author publications

    Search author on:PubMed Google Scholar

Rights and permissions

From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/

Reprints and permissions

About this article

Cite this article

Soldes, O., Kuick, R., Thompson II, I. et al. Differential expression of Hsp27 in normal oesophagus, Barrett’s metaplasia and oesophageal adenocarcinomas. Br J Cancer 79, 595–603 (1999). https://doi.org/10.1038/sj.bjc.6690094

Download citation

  • Received: 17 February 1998

  • Revised: 24 April 1998

  • Accepted: 06 May 1998

  • Published: 14 January 1999

  • Issue date: 01 February 1999

  • DOI: https://doi.org/10.1038/sj.bjc.6690094

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

Keywords

  • heat shock protein 27
  • Barrett’s metaplasia
  • oesophagus
  • cancer
  • adenocarcinoma

This article is cited by

  • Galectin-3 expression is prognostic in diffuse type gastric adenocarcinoma, confers aggressive phenotype, and can be targeted by YAP1/BET inhibitors

    • Jaffer A Ajani
    • Jeannelyn S Estrella
    • Shumei Song

    British Journal of Cancer (2018)

  • Nuclear expression of Gli-1 is predictive of pathologic complete response to chemoradiation in trimodality treated oesophageal cancer patients

    • Roopma Wadhwa
    • Xuemei Wang
    • Jaffer A Ajani

    British Journal of Cancer (2017)

  • The Functions of Antioxidants and Heat Shock Proteins Are Altered in the Immune Organs of Selenium-Deficient Broiler Chickens

    • Zijiang Yang
    • Ci Liu
    • Shu Li

    Biological Trace Element Research (2016)

  • Hsp27 (HSPB1) differential expression in normal salivary glands and pleomorphic adenomas and association with an increased Bcl2/Bax ratio

    • Elisa C. de Siqueira
    • Fabrício T. A. Souza
    • Carolina C. Gomes

    Tumor Biology (2015)

  • A mouse model for triple-negative breast cancer tumor-initiating cells (TNBC-TICs) exhibits similar aggressive phenotype to the human disease

    • Punit Kaur
    • Ganachari M Nagaraja
    • Alexzander Asea

    BMC Cancer (2012)

Download PDF

Advertisement

Explore content

  • Research articles
  • Reviews & Analysis
  • News & Comment
  • Current issue
  • Collections
  • Follow us on Twitter
  • Sign up for alerts
  • RSS feed

About the journal

  • Journal Information
  • Open access publishing
  • About the Editors
  • Contact
  • Special Issues
  • For Advertisers
  • Subscribe

Publish with us

  • For Authors & Referees
  • Language editing services
  • Submit manuscript

Search

Advanced search

Quick links

  • Explore articles by subject
  • Find a job
  • Guide to authors
  • Editorial policies

British Journal of Cancer (Br J Cancer)

ISSN 1532-1827 (online)

ISSN 0007-0920 (print)

nature.com sitemap

About Nature Portfolio

  • About us
  • Press releases
  • Press office
  • Contact us

Discover content

  • Journals A-Z
  • Articles by subject
  • protocols.io
  • Nature Index

Publishing policies

  • Nature portfolio policies
  • Open access

Author & Researcher services

  • Reprints & permissions
  • Research data
  • Language editing
  • Scientific editing
  • Nature Masterclasses
  • Research Solutions

Libraries & institutions

  • Librarian service & tools
  • Librarian portal
  • Open research
  • Recommend to library

Advertising & partnerships

  • Advertising
  • Partnerships & Services
  • Media kits
  • Branded content

Professional development

  • Nature Awards
  • Nature Careers
  • Nature Conferences

Regional websites

  • Nature Africa
  • Nature China
  • Nature India
  • Nature Japan
  • Nature Middle East
  • Privacy Policy
  • Use of cookies
  • Legal notice
  • Accessibility statement
  • Terms & Conditions
  • Your US state privacy rights
Springer Nature

© 2025 Springer Nature Limited