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Underexpression of Mineralocorticoid Receptor in Colorectal Carcinomas and Association with VEGFR-2 Overexpression

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Journal of Gastrointestinal Surgery Aims and scope

Abstract

Background

The human mineralocorticoid receptor (MR) is a steroid receptor widely expressed in colorectal mucosa. A significant role for the MR in the reduction of vascular endothelial growth factor receptor-2 (VEGFR-2) mRNA levels has been demonstrated in vitro. To evaluate a potential contribution of MR to colorectal carcinoma progression, we analyzed the expression of MR in relation to VEGFR-2.

Methods

Fresh human colorectal cancer tissue and adjacent normal mucosa were harvested from 48 consecutive patients. MR and VEGFR-2 mRNA expression levels were determined by real-time reverse transcriptase–polymerase chain reaction and correlated with clinicopathological parameters.

Results

A decline of MR expression was observed in all carcinomas compared to normal mucosa. Expression of MR was a median of 11-fold lower in carcinoma compared to the normal mucosa, irrespective of the location, size, stage, and differentiation. MR was a median of 20-fold underexpressed in carcinomas with VEGFR-2 overexpression vs only 9-fold in carcinomas with VEGFR-2 underexpression (p = 0.035, Mann–Whitney test).

Conclusions

These findings support the hypothesis that reduction of MR expression may be one of the early events involved in colorectal carcinoma progression. The inverse association between MR and VEGFR-2 expression in carcinoma suggests a potential tumor-suppressive function for MR.

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Acknowledgements

The authors wish to thank Carmela Masella, Lianna Mantley, and Rita Notte for their valuable secretarial assistance in the course of this study.

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Authors and Affiliations

  1. Department of Colon and Rectal Surgery, Sir Mortimer B. Davis Jewish General Hospital, Montreal, Quebec, Canada

    Francesco Di Fabio & Philip H. Gordon

  2. Department of Endocrinology, Sir Mortimer B. Davis Jewish General Hospital, Montreal, Quebec, Canada

    Agnieszka Majdan, Linda Voda, Lenore K. Beitel & Mark Trifiro

  3. Department of Pathology, Sir Mortimer B. Davis Jewish General Hospital, Montreal, Quebec, Canada

    Adrian Gologan

  4. Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, 3999 Cote St. Catherine Road, Montreal, Quebec, H3T 1E2, Canada

    Francesco Di Fabio, Carlos Alvarado, Agnieszka Majdan, Linda Voda, Elliot Mitmaker, Lenore K. Beitel & Mark Trifiro

  5. Department of Human Genetics, McGill University, Montreal, Quebec, Canada

    Lenore K. Beitel & Mark Trifiro

  6. Department of Medicine, McGill University, Montreal, Quebec, Canada

    Lenore K. Beitel & Mark Trifiro

  7. Cattedra di Chirurgia Generale, University of Brescia School of Medicine, Brescia, Italy

    Francesco Di Fabio

Authors
  1. Francesco Di Fabio
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  2. Carlos Alvarado
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  3. Agnieszka Majdan
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  4. Adrian Gologan
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  5. Linda Voda
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  7. Lenore K. Beitel
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  8. Philip H. Gordon
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  9. Mark Trifiro
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Correspondence to Francesco Di Fabio.

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Di Fabio, F., Alvarado, C., Majdan, A. et al. Underexpression of Mineralocorticoid Receptor in Colorectal Carcinomas and Association with VEGFR-2 Overexpression. J Gastrointest Surg 11, 1521–1528 (2007). https://doi.org/10.1007/s11605-007-0234-8

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  • DOI: https://doi.org/10.1007/s11605-007-0234-8

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