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Carcinogenesis Advance Access originally published online on April 29, 2004
Carcinogenesis 2004 25(9):1681-1688; doi:10.1093/carcin/bgh176
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Carcinogenesis vol.25 no.9 © Oxford University Press 2004; all rights reserved.

ARTICLE

Age-associated changes in the expression pattern of cyclooxygenase-2 and related apoptotic markers in the cancer susceptible region of rat prostate

Alaa F. Badawi1,4, Yingying Liu1, Mazen B. Eldeen1, Willard Morrow2, Zaineb R. Razak1, Marie Maradeo1 and Mostafa Z. Badr3

1 Division of Population Science, Fox Chase Cancer Center, Philadelphia, PA 19111, 2 Department of Basic Medical Science, School of Medicine and 3 Division of Pharmacology, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO 64108, USA

4 To whom correspondence should be addressed Email: af_badawi{at}fccc.edu

Senescence-associated changes in the prostate are believed to play an important role in the genesis of prostate cancer. In order to provide further information on how aging increases the prostate susceptibility to cancer, we examined the pattern of cyclooxygenase (COX)-2 expression and the concomitant alterations in prostaglandin E2 (PGE2) synthesis in the prostate glands of 4-, 10-, 50- and 100-week-old Fischer 344 rats. This was carried out in the prostatic areas where hormone-induced tumors arise, namely the periurethral ducts of the dorsolateral prostate (DLP). Age-associated changes were also evaluated for pro- and anti-apoptotic factors linked to COX-2 signaling and known to be involved in the normal development of the prostate gland as well as in carcinogenesis. COX-2 expression was increased in the DLP in an age-dependent manner where senescent rats had >3–4-fold higher COX-2 mRNA and protein levels than their juvenile counterparts (P<0.05). The age-related changes in COX-2 were accompanied by a similar up-regulation in the PGE2 synthesis. Evaluation of mediators of apoptotic signaling showed a significant (P<0.05) decline in the expression levels of the pro-apoptotic BAX (>6-fold) and peroxisome proliferator-activated receptor {gamma} (>3-fold) and in caspase-3 activity (>2-fold) and an up-regulation of the anti-apoptotic Bcl2 (>8-fold), PKC{alpha} (>2-fold) and pAkt (>4-fold) in the 100-week-old rats versus the 4-week-old animals. There was an ~15-fold age-dependent decrease in the pro-apoptotic ratio BAX:Bcl2 and an increase in the anti-apoptotic variable PKC{alpha}*Bcl2/BAX in the senescent rats compared with the juvenile ones. These results suggest that increased COX-2 expression can be linked to the decline in the pro-apoptotic signaling in the prostate gland during aging. Subsequently, COX-2 inhibitors can be considered as a promising class of agents to attenuate the increased cell survival and, hence, protect against tumorigenesis in the aging prostate.


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Related articles in Carcinogenesis:

Age-associated changes in the expression pattern of cyclooxygenase-2 and related apoptotic markers in the cancer susceptible region of rat prostate
Alaa F. Badawi, Yingying Liu, Mazen B. Eldeen, Willard Morrow, Zaineb R. Razak, Marie Maradeo, and Mostafa Z. Badr
Carcinogenesis 2005 26: 1650. [Extract] [FREE Full Text]  





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