title: Underexpression of mineralocorticoid receptor in colorectal carcinomas and association with VEGFR-2 overexpression.
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.
authors: Department of Colon and Rectal Surgery, Sir Mortimer B. Davis Jewish General Hospital, Montreal, Quebec, Canada. difabiof@hotmail.it
authors: Francesco
authors: F
authors: Di Fabio
authors: Carlos
authors: C
authors: Alvarado
authors: Agnieszka
authors: A
authors: Majdan
authors: Adrian
authors: A
authors: Gologan
authors: Linda
authors: L
authors: Voda
authors: Elliot
authors: E
authors: Mitmaker
authors: Lenore K
authors: LK
authors: Beitel
authors: Philip H
authors: PH
authors: Gordon
authors: Mark
authors: M
authors: Trifiro
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002454:Cell Differentiation; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D018161:Receptors, Mineralocorticoid / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D018161:Receptors, Mineralocorticoid; D040301:Vascular Endothelial Growth Factor Receptor-2
references: J Surg Res. 2001 Aug;99(2):222-7
references: 11469890
references: Cancer Res. 2006 Jan 15;66(2):632-7
references: 16423989
references: Nature. 1995 Jul 6;376(6535):62-6
references: 7596435
references: Pharmacol Rev. 2000 Jun;52(2):237-68
references: 10835101
references: Hypertension. 2004 May;43(5):938-40
references: 15007036
references: J Pathol. 2003 Jun;200(2):183-94
references: 12754739
references: J Clin Oncol. 2005 Feb 10;23(5):1011-27
references: 15585754
references: Circulation. 1996 Nov 15;94(10):2566-71
references: 8921802
references: Hypertension. 2006 Mar;47(3):312-8
references: 16432039
references: Vascul Pharmacol. 2004 Jan;40(6):269-77
references: 15063830
references: J Steroid Biochem Mol Biol. 2003 Jun;85(2-5):389-96
references: 12943727
references: Histol Histopathol. 2000 Jan;15(1):325-34
references: 10668221
references: Breast Cancer Res Treat. 1995;36(2):139-55
references: 8534863
references: Acta Physiol (Oxf). 2006 May-Jun;187(1-2):305-12
references: 16734767
references: J Natl Cancer Inst. 1990 Jan 3;82(1):4-6
references: 1688381
references: Nat Med. 2003 Jun;9(6):669-76
references: 12778165
references: J Mol Diagn. 2006 May;8(2):193-201
references: 16645205
references: Hypertension. 2006 Sep;48(3):490-6
references: 16847146
references: Nat Rev Mol Cell Biol. 2006 May;7(5):359-71
references: 16633338
references: Br J Cancer. 2005 Oct 17;93(8):855-8
references: 16189517
references: Circulation. 2002 Dec 3;106(23):2967-72
references: 12460880
references: J Cardiovasc Pharmacol. 2006 Apr;47(4):609-13
references: 16680076
references: Eur J Cancer. 2006 Jan;42(1):112-7
references: 16321517
references: Anticancer Res. 1998 Sep-Oct;18(5A):3381-8
references: 9858912
references: Am J Physiol Gastrointest Liver Physiol. 2002 May;282(5):G742-6
references: 11960770
references: J Hypertens. 2006 Nov;24(11):2207-13
references: 17053542
references: J Membr Biol. 2003 Dec 1;196(3):163-72
references: 14724742
references: Cell. 1994 Oct 21;79(2):185-8
references: 7525076