Article

Lab Invest 2003, 83:743–757

Age-Associated Changes in Histology and Gene-Expression Profile in the Rat Ventral Prostate

Current address for Dr. Lau: Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, New Territories, Hong Kong, SAR.

Current address for Dr. Cheng: Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, NIH, Building 538, Room 206, Frederick, Maryland 21702.

Current address for Dr. Thompson: CIIT Centers for Health Research, 6 Davis Drive, POB 12137, Research Triangle Park, North Carolina 27709-2137.

Kin-Mang Lau1, Neville N C Tam1, Christopher Thompson1, Robert Y S Cheng1, Yuet-Kin Leung1 and Shuk-Mei Ho1

1Department of Surgery, Division of Urology, University of Massachusetts Medical School, Worcester, Massachusetts

Correspondence: Dr. Shuk-Mei Ho, Rm 504, Lazare Research Building, Department of Surgery, University of Massachusetts Medical School, 364 Plantation Street, Worcester, Massachusetts 01605. E-mail: Shuk-mei.Ho@umassmed.edu

Received 13 March 2003.

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Abstract

The incidence of prostate diseases rises dramatically with age in men, yet little is understood of the mechanisms underlying prostatic senescence and its contribution to disease development in the gland. In Noble rats, aging of the ventral prostate (VP) is characterized morphologically by widespread atrophy of acini, increased accumulation of concretions in glandular lumen, infiltration of inflammatory cells, and focal epithelial atypia. We used a cDNA microarray containing 2388 known transcripts, together with the Tyramide Amplification System and t statistics, to identify differentially expressed genes in the VPs of young (3 months old) and old (16 months old) rats. A total of 78 VP genes were found to be differentially expressed by the two groups; in old rats, 65 VP genes (83%) showed reduced expression and 13 genes (17%) showed increased expression compared with young animals. The age-dependent underexpressed genes fell into several functional clusters: those involved in amino-acid metabolism, protein synthesis, protein secretion and degradation, vesicle/membrane trafficking, energy metabolism, signal transduction, spermidine and spermine syntheses, and cellular defense against stress. The overexpressed genes included iduronate 2-sulfatase, HLA class I locus C heavy chain, membrane cofactor protein of the complement system, TRPM-2, cadherin-associated protein-related, and X-CGD. Post hoc analyses confirmed a progressive decline in the expression of ribophorin II and BiP and a gradual increase in the expression of TRPM-2 in rat VPs as animals aged from 3 to 19 months old. In conclusion, the observed widespread declines in expression of genes involved in protein synthesis, protein fidelity maintenance, anabolism, growth inhibition, and energy metabolism, together with increased expression of genes implicated in cell survival in the VPs of senescent rats, may help explain the susceptibility of the prostates of elderly men to development of disease.