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mRNA expression of adipocytokines and glucocorticoid-related genes are associated with downregulation of E-cadherin mRNA in colorectal adenocarcinomas

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Abstract

Background

There is a consistently reported relationship between the incidence of colon cancer and obesity. It is thought that adipose tissue, particularly visceral fat, which secretes systemic factors that alter immunological, metabolic and endocrine milieu and promotes insulin resistance by producing adipocytokines, is important in cancer progression. Systemic high concentrations of adipocytokines, such as tumour necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), and glucocorticoid metabolism-related genes have been associated with gastrointestinal cancer. However, limited information exists about the expression of these cytokines within tumour tissue.

Material and methods

mRNA expression of TNF-α, IL-6,IL-8, IL-10, IL-1RN, glucocorticoid receptor alpha (GR-α), 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), plasminogen activator inhibitor-1 (PAI-1), Slug, vimentin, Snail and E-cadherin was analysed in paired samples of tumour tissue and normal mucosa in 60 surgical patients for Dukes B and C colorectal adenocarcinomas using quantitative reverse transcription PCR and microarray technology. The mRNA expression level of analysed genes was compared between tumour tissue and normal mucosa from the same patients, and a correlation to mRNA expression of E-cadherin in the same tissue samples was also performed.

Results

A highly significant difference in mRNA expression level of several of the analysed genes was observed between tumour tissue and the normal intestinal mucosa. Inverse correlation between mRNA expression of 11βHSD1, IL-6, GR-α and PAI-1 on one hand and mRNA expression of E-cadherin on the other hand was observed.

Conclusion

Results show that the adipocytokines and glucocorticoid metabolism-related genes are overexpressed in colorectal adenocarcinomas, and expression of these genes is associated with the downregulation of E-cadherin mRNA, connecting these genes to carcinogenesis and progression of colorectal cancer.

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Acknowledgments

This work was supported with grants from Southern and Eastern Norway Regional Health Authority and Østfold Hospital Trust. Torkil Pettersen, MD and Arvid Stordahl, MD were supported by Østfold Hospital Trust, Surgical Department, 1600 Fredrikstad, Norway. Ole Christian Olsen, MD received support from Buskerud Hospital Trust, Surgical Department, 3004 Drammen, Norway and Jan Godøy, MD from Akershus University Hospital, Dept. of Pathology, 1474 Lørenskog, Norway.

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Authors and Affiliations

  1. Surgical Department, Østfold Hospital Trust, 1600, Fredrikstad, Norway

    Ragnhild H. Størkson

  2. Surgical Department, Akershus University Hospital, 1474, Lørenskog, Norway

    Rolf Aamodt, Katja Kannisto Vetvik & Ida R. K. Bukholm

  3. Institute of Clinical Medicine, Akershus University Hospital, University of Oslo, 0316, Oslo, Norway

    Hilde S. Vollan & Ida R. K. Bukholm

  4. Department of Clinical Molecular Biology and Laboratory Sciences (EpiGen), Institute of Clinical Medicine, Akershus University Hospital, University of Oslo, 0316, Oslo, Norway

    Kristin Jonsdottir, Hilde S. Vollan, Tonje Sonerud & Torben Lüders

  5. Faculty Division Østfold Hospital Trust, R&D, Faculty of Medicine University of Oslo, 1600, Fredrikstad, Norway

    Morten B. Jacobsen

  6. Faculty of Medicine University of Oslo, Rikshospitalet, Oslo, Norway

    Morten B. Jacobsen

  7. Institute of Health Promotion, Akershus University Hospital, Lørenskog, Norway

    Geir Bukholm & Ida R. K. Bukholm

  8. Obesity Research Unit, Department of Medicine, Division of Internal Medicine, Helsinki University Central Hospital, PO Box 700, 00029, Helsinki, Finland

    Kirsi Pietilainen

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  1. Ragnhild H. Størkson
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  2. Rolf Aamodt
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  11. Ida R. K. Bukholm
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Corresponding author

Correspondence to Ida R. K. Bukholm.

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Størkson, R.H., Aamodt, R., Vetvik, K.K. et al. mRNA expression of adipocytokines and glucocorticoid-related genes are associated with downregulation of E-cadherin mRNA in colorectal adenocarcinomas. Int J Colorectal Dis 27, 1021–1027 (2012). https://doi.org/10.1007/s00384-012-1442-6

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  • DOI: https://doi.org/10.1007/s00384-012-1442-6

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