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Age-associated changes in the expression pattern of cyclooxygenase-2 and related apoptotic markers in the cancer susceptible region of rat prostate.
Carcinogenesis. 2004 Sep; 25(9):1681-8.C

Abstract

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 E(2) (PGE(2)) 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 PGE(2) 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 Bcl(2) (>8-fold), PKCalpha (>2-fold) and pAkt (>4-fold) in the 100-week-old rats versus the 4-week-old animals. There was an approximately 15-fold age-dependent decrease in the pro-apoptotic ratio BAX:Bcl(2) and an increase in the anti-apoptotic variable PKCalpha(*)Bcl(2)/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.

Authors+Show Affiliations

Division of Population Science, Fox Chase Cancer Center, Philadelphia, PA 19111, USA. af_badawi@fccc.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15117812

Citation

Badawi, Alaa F., et al. "Age-associated Changes in the Expression Pattern of Cyclooxygenase-2 and Related Apoptotic Markers in the Cancer Susceptible Region of Rat Prostate." Carcinogenesis, vol. 25, no. 9, 2004, pp. 1681-8.
Badawi AF, Liu Y, Eldeen MB, et al. Age-associated changes in the expression pattern of cyclooxygenase-2 and related apoptotic markers in the cancer susceptible region of rat prostate. Carcinogenesis. 2004;25(9):1681-8.
Badawi, A. F., Liu, Y., Eldeen, M. B., Morrow, W., Razak, Z. R., Maradeo, M., & Badr, M. Z. (2004). Age-associated changes in the expression pattern of cyclooxygenase-2 and related apoptotic markers in the cancer susceptible region of rat prostate. Carcinogenesis, 25(9), 1681-8.
Badawi AF, et al. Age-associated Changes in the Expression Pattern of Cyclooxygenase-2 and Related Apoptotic Markers in the Cancer Susceptible Region of Rat Prostate. Carcinogenesis. 2004;25(9):1681-8. PubMed PMID: 15117812.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Age-associated changes in the expression pattern of cyclooxygenase-2 and related apoptotic markers in the cancer susceptible region of rat prostate. AU - Badawi,Alaa F, AU - Liu,Yingying, AU - Eldeen,Mazen B, AU - Morrow,Willard, AU - Razak,Zaineb R, AU - Maradeo,Marie, AU - Badr,Mostafa Z, Y1 - 2004/04/29/ PY - 2004/5/1/pubmed PY - 2004/10/6/medline PY - 2004/5/1/entrez SP - 1681 EP - 8 JF - Carcinogenesis JO - Carcinogenesis VL - 25 IS - 9 N2 - 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 E(2) (PGE(2)) 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 PGE(2) 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 Bcl(2) (>8-fold), PKCalpha (>2-fold) and pAkt (>4-fold) in the 100-week-old rats versus the 4-week-old animals. There was an approximately 15-fold age-dependent decrease in the pro-apoptotic ratio BAX:Bcl(2) and an increase in the anti-apoptotic variable PKCalpha(*)Bcl(2)/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. SN - 0143-3334 UR - https://www.unboundmedicine.com/medline/citation/15117812/Age_associated_changes_in_the_expression_pattern_of_cyclooxygenase_2_and_related_apoptotic_markers_in_the_cancer_susceptible_region_of_rat_prostate_ L2 - https://academic.oup.com/carcin/article-lookup/doi/10.1093/carcin/bgh176 DB - PRIME DP - Unbound Medicine ER -