Underexpression of mineralocorticoid receptor in colorectal carcinomas and association with VEGFR-2 overexpression.
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.
Di Fabio
Francesco
F
Department of Colon and Rectal Surgery, Sir Mortimer B. Davis Jewish General Hospital, Montreal, Quebec, Canada. difabiof@hotmail.it
Alvarado
Carlos
C
Majdan
Agnieszka
A
Gologan
Adrian
A
Voda
Linda
L
Mitmaker
Elliot
E
Beitel
Lenore K
LK
Gordon
Philip H
PH
Trifiro
Mark
M
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*
D012333:RNA, Messenger; D018161:Receptors, Mineralocorticoid; D040301:Vascular Endothelial Growth Factor Receptor-2
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